Author: "Korst R." - Searchworks@Jio Institute Digital Library Search Results

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1. Oncogenic signaling pathways in the Cancer Genome Atlas

Author: Sanchez-Vega, F., Mina, M., Armenia, J., Chatila, W. K., Luna, A., La, K. C., Dimitriadoy, S., Liu, D. L., Kantheti, H. S., Saghafinia, S., Chakravarty, D., Daian, F., Gao, Q., Bailey, M. H., Liang, W. -W., Foltz, S. M., Shmulevich, I., Ding, L., Heins, Z., Ochoa, A., Gross, B., Gao, J., Zhang, H., Kundra, R., Kandoth, C., Bahceci, I., Dervishi, L., Doğrusöz, Uğur, Zhou, W., Shen, H., Laird, P. W., Way, G. P., Greene, C. S., Liang, H., Xiao, Y., Wang, C., Iavarone, A., Berger, A. H., Bivona, T. G., Lazar, A. J., Hammer, G. D., Giordano, T., Kwong, L. N., McArthur, G., Huang, C., Tward, A. D., Frederick, M. J., McCormick, F., Meyerson, M., Caesar-Johnson, S. J., Demchok, J. A., Felau, I., Kasapi, M., Ferguson, M. L., Hutter, C. M., Sofia, H. J., Tarnuzzer, R., Wang, Z., Yang, L., Zenklusen, J. C., Zhang, J. J., Chudamani, S., Liu, J., Lolla, L., Naresh, R., Pihl, T., Sun, Q., Wan, Y., Wu, Y., Cho, J., DeFreitas, T., Frazer, S., Gehlenborg, N., Getz, G., Heiman, D. I., Kim, J., Lawrence, M. S., Lin, P., Meier, S., Noble, M. S., Saksena, G., Voet, D., Bernard, B., Chambwe, N., Dhankani, V., Knijnenburg, T., Kramer, R., Leinonen, K., Liu, Y., Miller, M., Reynolds, S., Thorsson, V., Zhang, W., Akbani, R., Broom, B. M., Hegde, A. M., Ju, Z., Kanchi, R. S., Korkut, A., Li, J., Ling, S., Liu W., Lu, Y., Mills, G. B., Ng, K. -S., Rao, A., Ryan, M., Wang, J., Weinstein, J. N., Zhang, J., Abeshouse, A., de, Bruijn, I., Gross, B. E., Heins, Z. J., La, K., Ladanyi, M., Nissan, M. G., Phillips, S. M., Reznik, E., Sander, C., Schultz, N., Sheridan, R., Sumer, S. O., Sun, Y., Taylor, B. S., Anur, P., Peto, M., Spellman, P., Benz, C., Stuart, J. M., Wong, C. K., Yau, C., Hayes, D. N., Parker, J. S., Wilkerson, M. D., Ally, A., Balasundaram, M., Bowlby, R., Brooks, D., Carlsen, R., Chuah, E., Dhalla, N., Holt, R., Jones, S. J. M., Kasaian, K., Lee, D., Ma, Y., Marra, M. A., Mayo, M., Moore, R. A., Mungall, A. J., Mungall, K., Robertson, A. G., Sadeghi, S., Schein, J. E., Sipahimalani, P., Tam, A., Thiessen, N., Tse, K., Wong, T., Berger, A. C., Beroukhim, R., Cherniack, A. D., Cibulskis, C., Gabriel, S. B., Gao, G. F., Ha, G., Schumacher, S. E., Shih, J., Kucherlapati, M. H., Kucherlapati, R. S., Baylin, S., Cope, L., Danilova, L., Bootwalla, M. S., Lai, P. H., Maglinte, D. T., Van, Den, Berg, D. J., Weisenberger, D. J., Auman, J. T., Balu, S., Bodenheimer, T., Fan, C., Hoadley, K. A., Hoyle, A. P., Jefferys, S. R., Jones, C. D., Meng, S., Mieczkowski, P. A., Mose, L. E., Perou, A. H., Perou, C. M., Roach, J., Shi, Y., Simons, J. V., Skelly, T., Soloway, M. G., Tan, D., Veluvolu, U., Fan, H., Hinoue, T., Bellair, M., Chang, K., Covington, K., Creighton, C. J., Dinh, H., Doddapaneni, H., Donehower, L. A., Drummond, J., Gibbs, R. A., Glenn, R., Hale, W., Han, Y., Hu, J., Korchina, V., Lee, S., Lewis, L., Li, W., Liu, X., Morgan, M., Morton, D., Muzny, D., Santibanez, J., Sheth, M., Shinbrot, E., Wang, L., Wang, M., Wheeler, D. A., Xi, L., Zhao, F., Hess, J., Appelbaum, E. L., Bailey, M., Cordes, M. G., Fronick, C. C., Fulton, L. A., Fulton, R. S., Mardis, E. R., McLellan, M. D., Miller, C. A., Schmidt, H. K., Wilson, R. K., Crain, D., Curley, E., Gardner, J., Lau, K., Mallery, D., Morris, S., Paulauskis, J., Penny, R., Shelton, C., Shelton, T., Sherman, M., Thompson, E., Yena, P., Bowen, J., Gastier-Foster, J. M., Gerken, M., Leraas, K. M., Lichtenberg, T. M., Ramirez, N. C., Wise, L., Zmuda, E., Corcoran, N., Costello, T., Hovens, C., Carvalho, A. L., de, Carvalho, A. C., Fregnani, J. H., Longatto-Filho, A., Reis, R. M., Scapulatempo-Neto, C., Silveira, H. C. S., Vidal, D. O., Burnette, A., Eschbacher, J., Hermes, B., Noss, A., Singh, R., Anderson, M. L., Castro, P. D., Ittmann, M., Huntsman, D., Kohl, B., Le, X., Thorp, R., Andry, C., Duffy, E. R., Lyadov, V., Paklina, O., Setdikova, G., Shabunin, A., Tavobilov, M., McPherson, C., Warnick, R., Berkowitz, R., Cramer, D., Feltmate, C., Horowitz, N., Kibel, A., Muto, M., Raut, C. P., Malykh, A., Barnholtz-Sloan, J. S., Barrett, W., Devine, K., Fulop, J., Ostrom, Q. T., Shimmel, K., Wolinsky, Y., Sloan, A. E., De, Rose, A., Giuliante, F., Goodman, M., Karlan, B. Y., Hagedorn, C. H., Eckman, J., Harr, J., Myers, J., Tucker, K., Zach, L. A., Deyarmin, B., Hu, H., Kvecher, L., Larson, C., Mural, R. J., Somiari, S., Vicha, A., Zelinka, T., Bennett, J., Iacocca, M., Rabeno, B., Swanson, P., Latour, M., Lacombe, L., Têtu, B., Bergeron, A., McGraw, M., Staugaitis, S. M., Chabot, J., Hibshoosh, H., Sepulveda, A., Su, T., Wang, T., Potapova, O., Voronina, O., Desjardins, L., Mariani, O., Roman-Roman, S., Sastre, X., Stern, M. -H., Cheng, F., Signoretti, S., Berchuck, A., Bigner, D., Lipp, E., Marks, J., McCall, S., McLendon, R., Secord, A., Sharp, A., Behera, M., Brat, D. J., Chen, A., Delman, K., Force, S., Khuri, F., Magliocca, K., Maithel, S., Olson, J. J., Owonikoko, T., Pickens, A., Ramalingam, S., Shin, D. M., Sica, G., Van, Meir, E. G., Eijckenboom, W., Gillis, A., Korpershoek, E., Looijenga, L., Oosterhuis, W., Stoop, H., van, Kessel, K. E., Zwarthoff, E. C., Calatozzolo, C., Cuppini, L., Cuzzubbo, S., DiMeco, F., Finocchiaro, G., Mattei, L., Perin, A., Pollo, B., Chen, C., Houck, J., Lohavanichbutr, P., Hartmann, A., Stoehr, C., Stoehr, R., Taubert, H., Wach, S., Wullich, B., Kycler, W., Murawa, D., Wiznerowicz, M., Chung, K., Edenfield, W. J., Martin, J., Baudin, E., Bubley, G., Bueno, R., De, Rienzo, A., Richards, W. G., Kalkanis, S., Mikkelsen, T., Noushmehr, H., Scarpace, L., Girard, N., Aymerich, M., Campo, E., Giné, E., Guillermo, A. L., Van, Bang, N., Hanh, P. T., Phu, B. D., Tang, Y., Colman, H., Evason, K., Dottino, P. R., Martignetti, J. A., Gabra, H., Juhl, H., Akeredolu, T., Stepa, S., Hoon, D., Ahn, K., Kang, K. J., Beuschlein, F., Breggia, A., Birrer, M., Bell, D., Borad, M., Bryce, A. H., Castle, E., Chandan, V., Cheville, J., Copland, J. A., Farnell, M., Flotte, T., Giama, N., Ho, T., Kendrick, M., Kocher, J. -P., Kopp, K., Moser, C., Nagorney, D., O'Brien, D., O'Neill, B. P., Patel, T., Petersen, G., Que, F., Rivera, M., Roberts, L., Smallridge, R., Smyrk, T., Stanton, M., Thompson, R. H., Torbenson, M., Yang, J. D., Zhang, L., Brimo, F., Ajani, J. A., Gonzalez, A. M. A., Behrens, C., Bondaruk, J., Broaddus, R., Czerniak, B., Esmaeli, B., Fujimoto, J., Gershenwald, J., Guo, C., Logothetis, C., Meric-Bernstam, F., Moran, C., Ramondetta, L., Rice, D., Sood, A., Tamboli, P., Thompson, T., Troncoso, P., Tsao, A., Wistuba, I., Carter, C., Haydu, L., Hersey, P., Jakrot, V., Kakavand, H., Kefford, R., Lee, K., Long, G., Mann, G., Quinn, M., Saw, R., Scolyer, R., Shannon, K., Spillane, A., Stretch, J., Synott, M., Thompson, J., Wilmott, J., Al-Ahmadie, H., Chan, T. A., Ghossein, R., Gopalan, A., Levine, D. A., Reuter, V., Singer, S., Singh, B., Tien, N. V., Broudy, T., Mirsaidi, C., Nair, P., Drwiega, P., Miller, J., Smith, J., Zaren, H., Park, J. -W., Hung, N. P., Kebebew, E., Linehan, W. M., Metwalli, A. R., Pacak, K., Pinto, P. A., Schiffman, M., Schmidt, L. S., Vocke, C. D., Wentzensen, N., Worrell, R., Yang, H., Moncrieff, M., Goparaju, C., Melamed, J., Pass, H., Botnariuc, N., Caraman, I., Cernat, M., Chemencedji, I., Clipca, A., Doruc, S., Gorincioi, G., Mura, S., Pirtac, M., Stancul, I., Tcaciuc, D., Albert, M., Alexopoulou, I., Arnaout, A., Bartlett, J., Engel, J., Gilbert, S., Parfitt, J., Sekhon, H., Thomas, G., Rassl, D. M., Rintoul, R. C., Bifulco, C., Tamakawa, R., Urba, W., Hayward, N., Timmers, H., Antenucci, A., Facciolo, F., Grazi, G., Marino, M., Merola, R., de, Krijger, R., Gimenez-Roqueplo, A. -P., Piché, A., Chevalier, S., McKercher, G., Birsoy, K., Barnett, G., Brewer, C., Farver, C., Naska, T., Pennell, N. A., Raymond, D., Schilero, C., Smolenski, K., Williams, F., Morrison, C., Borgia, J. A., Liptay, M. J., Pool, M., Seder, C. W., Junker, K., Omberg, L., Dinkin, M., Manikhas, G., Alvaro, D., Bragazzi, M. C., Cardinale, V., Carpino, G., Gaudio, E., Chesla, D., Cottingham, S., Dubina, M., Moiseenko, F., Dhanasekaran, R., Becker, K. -F., Janssen, K. -P., Slotta-Huspenina, J., Abdel-Rahman, M. H., Aziz, D., Bell, S., Cebulla, C. M., Davis, A., Duell, R., Elder, J. B., Hilty, J., Kumar, B., Lang, J., Lehman, N. L., Mandt, R., Nguyen, P., Pilarski, R., Rai, K., Schoenfield, L., Senecal, K., Wakely, P., Hansen, P., Lechan, R., Powers, J., Tischler, A., Grizzle, W. E., Sexton, K. C., Kastl, A., Henderson, J., Porten, S., Waldmann, J., Fassnacht, M., Asa, S. L., Schadendorf, D., Couce, M., Graefen, M., Huland, H., Sauter, G., Schlomm, T., Simon, R., Tennstedt, P., Olabode, O., Nelson, M., Bathe, O., Carroll, P. R., Chan, J. M., Disaia, P., Glenn, P., Kelley, R. K., Landen, C. N., Phillips, J., Prados, M., Simko, J., Smith-McCune, K., VandenBerg, S., Roggin, K., Fehrenbach, A., Kendler, A., Sifri, S., Steele, R., Jimeno, A., Carey, F., Forgie, I., Mannelli, M., Carney, M., Hernandez, B., Campos, B., Herold-Mende, C., Jungk, C., Unterberg, A., von, Deimling, A., Bossler, A., Galbraith, J., Jacobus, L., Knudson, M., Knutson, T., Ma, D., Milhem, M., Sigmund, R., Godwin, A. K., Madan, R., Rosenthal, H. G., Adebamowo, C., Adebamowo, S. N., Boussioutas, A., Beer, D., Mes-Masson, A. -M., Saad, F., Bocklage, T., Landrum, L., Mannel, R., Moore, K., Moxley, K., Postier, R., Walker, J., Zuna, R., Feldman, M., Valdivieso, F., Dhir, R., Luketich, J., Pinero, E. M. M., Quintero-Aguilo, M., Carlotti, C. G., Jr., Dos, Santos, J. S., Kemp, R., Sankarankuty, A., Tirapelli, D., Catto, J., Agnew, K., Swisher, E., Creaney, J., Robinson, B., Shelley, C. S., Godwin, E. M., Kendall, S., Shipman, C., Bradford, C., Carey, T., Haddad, A., Moyer, J., Peterson, L., Prince, M., Rozek, L., Wolf, G., Bowman, R., Fong, K. M., Yang, I., Korst, R., Rathmell, W. K., Fantacone-Campbell, J. L., Hooke, J. A., Kovatich, A. J., Shriver, C. D., DiPersio, J., Drake, B., Govindan, R., Heath, S., Ley, T., Van, Tine, B., Westervelt, P., Rubin, M. A., Lee, J. I., Aredes, N. D., Mariamidze, A., Van, Allen, E. M., Ciriello, G., The, Cancer, Genome, Atlas, Research, Network.tif, Doğrusöz, Uğur, Cancer Genome Atlas Research Network, Caesar-Johnson, S.J., Demchok, J.A., Felau, I., Kasapi, M., Ferguson, M.L., Hutter, C.M., Sofia, H.J., Tarnuzzer, R., Wang, Z., Yang, L., Zenklusen, J.C., Zhang, J.J., Chudamani, S., Liu, J., Lolla, L., Naresh, R., Pihl, T., Sun, Q., Wan, Y., Wu, Y., Cho, J., DeFreitas, T., Frazer, S., Gehlenborg, N., Getz, G., Heiman, D.I., Kim, J., Lawrence, M.S., Lin, P., Meier, S., Noble, M.S., Saksena, G., Voet, D., Zhang, H., Bernard, B., Chambwe, N., Dhankani, V., Knijnenburg, T., Kramer, R., Leinonen, K., Liu, Y., Miller, M., Reynolds, S., Shmulevich, I., Thorsson, V., Zhang, W., Akbani, R., Broom, B.M., Hegde, A.M., Ju, Z., Kanchi, R.S., Korkut, A., Li, J., Liang, H., Ling, S., Liu, W., Lu, Y., Mills, G.B., Ng, K.S., Rao, A., Ryan, M., Wang, J., Weinstein, J.N., Zhang, J., Abeshouse, A., Armenia, J., Chakravarty, D., Chatila, W.K., de Bruijn, I., Gao, J., Gross, B.E., Heins, Z.J., Kundra, R., La, K., Ladanyi, M., Luna, A., Nissan, M.G., Ochoa, A., Phillips, S.M., Reznik, E., Sanchez-Vega, F., Sander, C., Schultz, N., Sheridan, R., Sumer, S.O., Sun, Y., Taylor, B.S., Anur, P., Peto, M., Spellman, P., Benz, C., Stuart, J.M., Wong, C.K., Yau, C., Hayes, D.N., Parker, J.S., Wilkerson, M.D., Ally, A., Balasundaram, M., Bowlby, R., Brooks, D., Carlsen, R., Chuah, E., Dhalla, N., Holt, R., Jones, SJM, Kasaian, K., Lee, D., Ma, Y., Marra, M.A., Mayo, M., Moore, R.A., Mungall, A.J., Mungall, K., Robertson, A.G., Sadeghi, S., Schein, J.E., Sipahimalani, P., Tam, A., Thiessen, N., Tse, K., Wong, T., Berger, A.C., Beroukhim, R., Cherniack, A.D., Cibulskis, C., Gabriel, S.B., Gao, G.F., Ha, G., Meyerson, M., Schumacher, S.E., Shih, J., Kucherlapati, M.H., Kucherlapati, R.S., Baylin, S., Cope, L., Danilova, L., Bootwalla, M.S., Lai, P.H., Maglinte, D.T., Van Den Berg, D.J., Weisenberger, D.J., Auman, J.T., Balu, S., Bodenheimer, T., Fan, C., Hoadley, K.A., Hoyle, A.P., Jefferys, S.R., Jones, C.D., Meng, S., Mieczkowski, P.A., Mose, L.E., Perou, A.H., Perou, C.M., Roach, J., Shi, Y., Simons, J.V., Skelly, T., Soloway, M.G., Tan, D., Veluvolu, U., Fan, H., Hinoue, T., Laird, P.W., Shen, H., Zhou, W., Bellair, M., Chang, K., Covington, K., Creighton, C.J., Dinh, H., Doddapaneni, H., Donehower, L.A., Drummond, J., Gibbs, R.A., Glenn, R., Hale, W., Han, Y., Hu, J., Korchina, V., Lee, S., Lewis, L., Li, W., Liu, X., Morgan, M., Morton, D., Muzny, D., Santibanez, J., Sheth, M., Shinbrot, E., Wang, L., Wang, M., Wheeler, D.A., Xi, L., Zhao, F., Hess, J., Appelbaum, E.L., Bailey, M., Cordes, M.G., Ding, L., Fronick, C.C., Fulton, L.A., Fulton, R.S., Kandoth, C., Mardis, E.R., McLellan, M.D., Miller, C.A., Schmidt, H.K., Wilson, R.K., Crain, D., Curley, E., Gardner, J., Lau, K., Mallery, D., Morris, S., Paulauskis, J., Penny, R., Shelton, C., Shelton, T., Sherman, M., Thompson, E., Yena, P., Bowen, J., Gastier-Foster, J.M., Gerken, M., Leraas, K.M., Lichtenberg, T.M., Ramirez, N.C., Wise, L., Zmuda, E., Corcoran, N., Costello, T., Hovens, C., Carvalho, A.L., de Carvalho, A.C., Fregnani, J.H., Longatto-Filho, A., Reis, R.M., Scapulatempo-Neto, C., Silveira, HCS, Vidal, D.O., Burnette, A., Eschbacher, J., Hermes, B., Noss, A., Singh, R., Anderson, M.L., Castro, P.D., Ittmann, M., Huntsman, D., Kohl, B., Le, X., Thorp, R., Andry, C., Duffy, E.R., Lyadov, V., Paklina, O., Setdikova, G., Shabunin, A., Tavobilov, M., McPherson, C., Warnick, R., Berkowitz, R., Cramer, D., Feltmate, C., Horowitz, N., Kibel, A., Muto, M., Raut, C.P., Malykh, A., Barnholtz-Sloan, J.S., Barrett, W., Devine, K., Fulop, J., Ostrom, Q.T., Shimmel, K., Wolinsky, Y., Sloan, A.E., De Rose, A., Giuliante, F., Goodman, M., Karlan, B.Y., Hagedorn, C.H., Eckman, J., Harr, J., Myers, J., Tucker, K., Zach, L.A., Deyarmin, B., Hu, H., Kvecher, L., Larson, C., Mural, R.J., Somiari, S., Vicha, A., Zelinka, T., Bennett, J., Iacocca, M., Rabeno, B., Swanson, P., Latour, M., Lacombe, L., Têtu, B., Bergeron, A., McGraw, M., Staugaitis, S.M., Chabot, J., Hibshoosh, H., Sepulveda, A., Su, T., Wang, T., Potapova, O., Voronina, O., Desjardins, L., Mariani, O., Roman-Roman, S., Sastre, X., Stern, M.H., Cheng, F., Signoretti, S., Berchuck, A., Bigner, D., Lipp, E., Marks, J., McCall, S., McLendon, R., Secord, A., Sharp, A., Behera, M., Brat, D.J., Chen, A., Delman, K., Force, S., Khuri, F., Magliocca, K., Maithel, S., Olson, J.J., Owonikoko, T., Pickens, A., Ramalingam, S., Shin, D.M., Sica, G., Van Meir, E.G., Eijckenboom, W., Gillis, A., Korpershoek, E., Looijenga, L., Oosterhuis, W., Stoop, H., van Kessel, K.E., Zwarthoff, E.C., Calatozzolo, C., Cuppini, L., Cuzzubbo, S., DiMeco, F., Finocchiaro, G., Mattei, L., Perin, A., Pollo, B., Chen, C., Houck, J., Lohavanichbutr, P., Hartmann, A., Stoehr, C., Stoehr, R., Taubert, H., Wach, S., Wullich, B., Kycler, W., Murawa, D., Wiznerowicz, M., Chung, K., Edenfield, W.J., Martin, J., Baudin, E., Bubley, G., Bueno, R., De Rienzo, A., Richards, W.G., Kalkanis, S., Mikkelsen, T., Noushmehr, H., Scarpace, L., Girard, N., Aymerich, M., Campo, E., Giné, E., Guillermo, A.L., Van Bang, N., Hanh, P.T., Phu, B.D., Tang, Y., Colman, H., Evason, K., Dottino, P.R., Martignetti, J.A., Gabra, H., Juhl, H., Akeredolu, T., Stepa, S., Hoon, D., Ahn, K., Kang, K.J., Beuschlein, F., Breggia, A., Birrer, M., Bell, D., Borad, M., Bryce, A.H., Castle, E., Chandan, V., Cheville, J., Copland, J.A., Farnell, M., Flotte, T., Giama, N., Ho, T., Kendrick, M., Kocher, J.P., Kopp, K., Moser, C., Nagorney, D., O'Brien, D., O'Neill, B.P., Patel, T., Petersen, G., Que, F., Rivera, M., Roberts, L., Smallridge, R., Smyrk, T., Stanton, M., Thompson, R.H., Torbenson, M., Yang, J.D., Zhang, L., Brimo, F., Ajani, J.A., Gonzalez, AMA, Behrens, C., Bondaruk, J., Broaddus, R., Czerniak, B., Esmaeli, B., Fujimoto, J., Gershenwald, J., Guo, C., Lazar, A.J., Logothetis, C., Meric-Bernstam, F., Moran, C., Ramondetta, L., Rice, D., Sood, A., Tamboli, P., Thompson, T., Troncoso, P., Tsao, A., Wistuba, I., Carter, C., Haydu, L., Hersey, P., Jakrot, V., Kakavand, H., Kefford, R., Lee, K., Long, G., Mann, G., Quinn, M., Saw, R., Scolyer, R., Shannon, K., Spillane, A., Stretch, J., Synott, M., Thompson, J., Wilmott, J., Al-Ahmadie, H., Chan, T.A., Ghossein, R., Gopalan, A., Levine, D.A., Reuter, V., Singer, S., Singh, B., Tien, N.V., Broudy, T., Mirsaidi, C., Nair, P., Drwiega, P., Miller, J., Smith, J., Zaren, H., Park, J.W., Hung, N.P., Kebebew, E., Linehan, W.M., Metwalli, A.R., Pacak, K., Pinto, P.A., Schiffman, M., Schmidt, L.S., Vocke, C.D., Wentzensen, N., Worrell, R., Yang, H., Moncrieff, M., Goparaju, C., Melamed, J., Pass, H., Botnariuc, N., Caraman, I., Cernat, M., Chemencedji, I., Clipca, A., Doruc, S., Gorincioi, G., Mura, S., Pirtac, M., Stancul, I., Tcaciuc, D., Albert, M., Alexopoulou, I., Arnaout, A., Bartlett, J., Engel, J., Gilbert, S., Parfitt, J., Sekhon, H., Thomas, G., Rassl, D.M., Rintoul, R.C., Bifulco, C., Tamakawa, R., Urba, W., Hayward, N., Timmers, H., Antenucci, A., Facciolo, F., Grazi, G., Marino, M., Merola, R., de Krijger, R., Gimenez-Roqueplo, A.P., Piché, A., Chevalier, S., McKercher, G., Birsoy, K., Barnett, G., Brewer, C., Farver, C., Naska, T., Pennell, N.A., Raymond, D., Schilero, C., Smolenski, K., Williams, F., Morrison, C., Borgia, J.A., Liptay, M.J., Pool, M., Seder, C.W., Junker, K., Omberg, L., Dinkin, M., Manikhas, G., Alvaro, D., Bragazzi, M.C., Cardinale, V., Carpino, G., Gaudio, E., Chesla, D., Cottingham, S., Dubina, M., Moiseenko, F., Dhanasekaran, R., Becker, K.F., Janssen, K.P., Slotta-Huspenina, J., Abdel-Rahman, M.H., Aziz, D., Bell, S., Cebulla, C.M., Davis, A., Duell, R., Elder, J.B., Hilty, J., Kumar, B., Lang, J., Lehman, N.L., Mandt, R., Nguyen, P., Pilarski, R., Rai, K., Schoenfield, L., Senecal, K., Wakely, P., Hansen, P., Lechan, R., Powers, J., Tischler, A., Grizzle, W.E., Sexton, K.C., Kastl, A., Henderson, J., Porten, S., Waldmann, J., Fassnacht, M., Asa, S.L., Schadendorf, D., Couce, M., Graefen, M., Huland, H., Sauter, G., Schlomm, T., Simon, R., Tennstedt, P., Olabode, O., Nelson, M., Bathe, O., Carroll, P.R., Chan, J.M., Disaia, P., Glenn, P., Kelley, R.K., Landen, C.N., Phillips, J., Prados, M., Simko, J., Smith-McCune, K., VandenBerg, S., Roggin, K., Fehrenbach, A., Kendler, A., Sifri, S., Steele, R., Jimeno, A., Carey, F., Forgie, I., Mannelli, M., Carney, M., Hernandez, B., Campos, B., Herold-Mende, C., Jungk, C., Unterberg, A., von Deimling, A., Bossler, A., Galbraith, J., Jacobus, L., Knudson, M., Knutson, T., Ma, D., Milhem, M., Sigmund, R., Godwin, A.K., Madan, R., Rosenthal, H.G., Adebamowo, C., Adebamowo, S.N., Boussioutas, A., Beer, D., Giordano, T., Mes-Masson, A.M., Saad, F., Bocklage, T., Landrum, L., Mannel, R., Moore, K., Moxley, K., Postier, R., Walker, J., Zuna, R., Feldman, M., Valdivieso, F., Dhir, R., Luketich, J., Pinero, EMM, Quintero-Aguilo, M., Carlotti, C.G., Dos Santos, J.S., Kemp, R., 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Taylor B.S., Anur P., Peto M., Spellman P., Benz C., Stuart J.M., Wong C.K., Yau C., Hayes D.N., Parker J.S., Wilkerson M.D., Ally A., Balasundaram M., Bowlby R., Brooks D., Carlsen R., Chuah E., Dhalla N., Holt R., Jones S.J.M., Kasaian K., Lee D., Ma Y., Marra M.A., Mayo M., Moore R.A., Mungall A.J., Mungall K., Robertson A.G., Sadeghi S., Schein J.E., Sipahimalani P., Tam A., Thiessen N., Tse K., Wong T., Berger A.C., Beroukhim R., Cherniack A.D., Cibulskis C., Gabriel S.B., Gao G.F., Ha G., Schumacher S.E., Shih J., Kucherlapati M.H., Kucherlapati R.S., Baylin S., Cope L., Danilova L., Bootwalla M.S., Lai P.H., Maglinte D.T., Van Den Berg D.J., Weisenberger D.J., Auman J.T., Balu S., Bodenheimer T., Fan C., Hoadley K.A., Hoyle A.P., Jefferys S.R., Jones C.D., Meng S., Mieczkowski P.A., Mose L.E., Perou A.H., Perou C.M., Roach J., Shi Y., Simons J.V., Skelly T., Soloway M.G., Tan D., Veluvolu U., Fan H., Hinoue T., Bellair M., Chang K., Covington K., Creighton C.J., Dinh H., Doddapaneni H., Donehower L.A., Drummond J., Gibbs R.A., Glenn R., Hale W., Han Y., Hu J., Korchina V., Lee S., Lewis L., Li W., Liu X., Morgan M., Morton D., Muzny D., Santibanez J., Sheth M., Shinbrot E., Wang L., Wang M., Wheeler D.A., Xi L., Zhao F., Hess J., Appelbaum E.L., Bailey M., Cordes M.G., Fronick C.C., Fulton L.A., Fulton R.S., Mardis E.R., McLellan M.D., Miller C.A., Schmidt H.K., Wilson R.K., Crain D., Curley E., Gardner J., Lau K., Mallery D., Morris S., Paulauskis J., Penny R., Shelton C., Shelton T., Sherman M., Thompson E., Yena P., Bowen J., Gastier-Foster J.M., Gerken M., Leraas K.M., Lichtenberg T.M., Ramirez N.C., Wise L., Zmuda E., Corcoran N., Costello T., Hovens C., Carvalho A.L., de Carvalho A.C., Fregnani J.H., Longatto-Filho A., Reis R.M., Scapulatempo-Neto C., Silveira H.C.S., Vidal D.O., Burnette A., Eschbacher J., Hermes B., Noss A., Singh R., Anderson M.L., Castro P.D., Ittmann M., Huntsman D., Kohl B., Le X., Thorp R., Andry C., Duffy E.R., Lyadov V., Paklina O., Setdikova G., Shabunin A., Tavobilov M., McPherson C., Warnick R., Berkowitz R., Cramer D., Feltmate C., Horowitz N., Kibel A., Muto M., Raut C.P., Malykh A., Barnholtz-Sloan J.S., Barrett W., Devine K., Fulop J., Ostrom Q.T., Shimmel K., Wolinsky Y., Sloan A.E., De Rose A., Giuliante F., Goodman M., Karlan B.Y., Hagedorn C.H., Eckman J., Harr J., Myers J., Tucker K., Zach L.A., Deyarmin B., Hu H., Kvecher L., Larson C., Mural R.J., Somiari S., Vicha A., Zelinka T., Bennett J., Iacocca M., Rabeno B., Swanson P., Latour M., Lacombe L., Tetu B., Bergeron A., McGraw M., Staugaitis S.M., Chabot J., Hibshoosh H., Sepulveda A., Su T., Wang T., Potapova O., Voronina O., Desjardins L., Mariani O., Roman-Roman S., Sastre X., Stern M.-H., Cheng F., Signoretti S., Berchuck A., Bigner D., Lipp E., Marks J., McCall S., McLendon R., Secord A., Sharp A., Behera M., Brat D.J., Chen A., Delman K., Force S., Khuri F., Magliocca K., Maithel S., Olson J.J., Owonikoko T., Pickens A., Ramalingam 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O'Brien D., O'Neill B.P., Patel T., Petersen G., Que F., Rivera M., Roberts L., Smallridge R., Smyrk T., Stanton M., Thompson R.H., Torbenson M., Yang J.D., Zhang L., Brimo F., Ajani J.A., Gonzalez A.M.A., Behrens C., Bondaruk J., Broaddus R., Czerniak B., Esmaeli B., Fujimoto J., Gershenwald J., Guo C., Logothetis C., Meric-Bernstam F., Moran C., Ramondetta L., Rice D., Sood A., Tamboli P., Thompson T., Troncoso P., Tsao A., Wistuba I., Carter C., Haydu L., Hersey P., Jakrot V., Kakavand H., Kefford R., Lee K., Long G., Mann G., Quinn M., Saw R., Scolyer R., Shannon K., Spillane A., Stretch J., Synott M., Thompson J., Wilmott J., Al-Ahmadie H., Chan T.A., Ghossein R., Gopalan A., Levine D.A., Reuter V., Singer S., Singh B., Tien N.V., Broudy T., Mirsaidi C., Nair P., Drwiega P., Miller J., Smith J., Zaren H., Park J.-W., Hung N.P., Kebebew E., Linehan W.M., Metwalli A.R., Pacak K., Pinto P.A., Schiffman M., Schmidt L.S., Vocke C.D., Wentzensen N., Worrell R., Yang H., Moncrieff M., Goparaju C., Melamed J., Pass H., Botnariuc N., Caraman I., Cernat M., Chemencedji I., Clipca A., Doruc S., Gorincioi G., Mura S., Pirtac M., Stancul I., Tcaciuc D., Albert M., Alexopoulou I., Arnaout A., Bartlett J., Engel J., Gilbert S., Parfitt J., Sekhon H., Thomas G., Rassl D.M., Rintoul R.C., Bifulco C., Tamakawa R., Urba W., Hayward N., Timmers H., Antenucci A., Facciolo F., Grazi G., Marino M., Merola R., de Krijger R., Gimenez-Roqueplo A.-P., Piche A., Chevalier S., McKercher G., Birsoy K., Barnett G., Brewer C., Farver C., Naska T., Pennell N.A., Raymond D., Schilero C., Smolenski K., Williams F., Morrison C., Borgia J.A., Liptay M.J., Pool M., Seder C.W., Junker K., Omberg L., Dinkin M., Manikhas G., Alvaro D., Bragazzi M.C., Cardinale V., Carpino G., Gaudio E., Chesla D., Cottingham S., Dubina M., Moiseenko F., Dhanasekaran R., Becker K.-F., Janssen K.-P., Slotta-Huspenina J., Abdel-Rahman M.H., Aziz D., Bell S., Cebulla C.M., Davis A., Duell R., Elder J.B., Hilty J., Kumar B., Lang J., Lehman N.L., Mandt R., Nguyen P., Pilarski R., Rai K., Schoenfield L., Senecal K., Wakely P., Hansen P., Lechan R., Powers J., Tischler A., Grizzle W.E., Sexton K.C., Kastl A., Henderson J., Porten S., Waldmann J., Fassnacht M., Asa S.L., Schadendorf D., Couce M., Graefen M., Huland H., Sauter G., Schlomm T., Simon R., Tennstedt P., Olabode O., Nelson M., Bathe O., Carroll P.R., Chan J.M., Disaia P., Glenn P., Kelley R.K., Landen C.N., Phillips J., Prados M., Simko J., Smith-McCune K., VandenBerg S., Roggin K., Fehrenbach A., Kendler A., Sifri S., Steele R., Jimeno A., Carey F., Forgie I., Mannelli M., Carney M., Hernandez B., Campos B., Herold-Mende C., Jungk C., Unterberg A., von Deimling A., Bossler A., Galbraith J., Jacobus L., Knudson M., Knutson T., Ma D., Milhem M., Sigmund R., Godwin A.K., Madan R., Rosenthal H.G., Adebamowo C., Adebamowo S.N., Boussioutas A., Beer D., Mes-Masson A.-M., Saad F., Bocklage T., Landrum L., Mannel R., Moore K., Moxley K., Postier R., Walker J., Zuna R., Feldman M., Valdivieso F., Dhir R., Luketich J., Pinero E.M.M., Quintero-Aguilo M., Carlotti C.G., Dos Santos J.S., Kemp R., Sankarankuty A., Tirapelli D., Catto J., Agnew K., Swisher E., Creaney J., Robinson B., Shelley C.S., Godwin E.M., Kendall S., Shipman C., Bradford C., Carey T., Haddad A., Moyer J., Peterson L., Prince M., Rozek L., Wolf G., Bowman R., Fong K.M., Yang I., Korst R., Rathmell W.K., Fantacone-Campbell J.L., Hooke J.A., Kovatich A.J., Shriver C.D., DiPersio J., Drake B., Govindan R., Heath S., Ley T., Van Tine B., Westervelt P., Rubin M.A., Lee J.I., Aredes N.D., Mariamidze A., Van Allen E.M., and Ciriello G.
Subjects: 0301 basic medicine, cancer genome atlas, cancer genomics, combination therapy, pan-cancer, PanCanAtlas, precision oncology, signaling pathways, TCGA, therapeutics, whole exome sequencing, Signaling pathways, Somatic cell, Wnt Protein, Cancer Genome Atlas Research Network, Biochemistry, Medical and Health Sciences, Phosphatidylinositol 3-Kinases, Transforming Growth Factor beta, Neoplasms, Databases, Genetic, LS2_1, Cancer genomics, LS4_6, 610 Medicine & health, 11 Medical and Health Sciences, Cancer, biology, Wnt signaling pathway, cancer genomic, Precision oncology, Biological Sciences, Cell cycle, DNA methylation, Signal transduction, CICLO CELULAR, Life Sciences & Biomedicine, Genes, Neoplasm, Humans, Neoplasms/genetics, Neoplasms/pathology, Phosphatidylinositol 3-Kinases/genetics, Phosphatidylinositol 3-Kinases/metabolism, Signal Transduction/genetics, Transforming Growth Factor beta/genetics, Transforming Growth Factor beta/metabolism, Tumor Suppressor Protein p53/genetics, Tumor Suppressor Protein p53/metabolism, Wnt Proteins/genetics, Wnt Proteins/metabolism, Biotechnology, Human, Signal Transduction, signaling pathway, EXPRESSION, Biochemistry & Molecular Biology, GENES, Pan-cancer, Therapeutics, General Biochemistry, Genetics and Molecular Biology, NO, Databases, 03 medical and health sciences, Genetic, Genetics, Combination therapy, Protein kinase B, Gene, SIGNATURES, Cancer genome atlas, Science & Technology, LANDSCAPE, MUTATIONS, Biochemistry, Genetics and Molecular Biology(all), Human Genome, Whole exome sequencing, Cell Biology, Transforming growth factor beta, cancer genome atla, 06 Biological Sciences, COMPREHENSIVE MOLECULAR CHARACTERIZATION, Wnt Proteins, therapeutic, Good Health and Well Being, 030104 developmental biology, Genes, PanCanAtla, biology.protein, Cancer research, Neoplasm, Phosphatidylinositol 3-Kinase, Tumor Suppressor Protein p53, Digestive Diseases, Genetics and Molecular Biology(all), Developmental Biology
Abstract: Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methylation in 9,125 tumors profiled by The Cancer Genome Atlas (TCGA), we analyzed the mechanisms and patterns of somatic alterations in ten canonical pathways: cell cycle, Hippo, Myc, Notch, Nrf2, PI-3-Kinase/Akt, RTK-RAS, TGFβ signaling, p53 and β-catenin/Wnt. We charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity. Eighty-nine percent of tumors had at least one driver alteration in these pathways, and 57% percent of tumors had at least one alteration potentially targetable by currently available drugs. Thirty percent of tumors had multiple targetable alterations, indicating opportunities for combination therapy. An integrated analysis of genetic alterations in 10 signaling pathways in >9,000 tumors profiled by TCGA highlights significant representation of individual and co-occurring actionable alterations in these pathways, suggesting opportunities for targeted and combination therapies. Michael Seiler, Peter G. Smith, Ping Zhu, Silvia Buonamici, and Lihua Yu are employees of H3 Biomedicine, Inc. Parts of this work are the subject of a patent application: WO2017040526 titled “Splice variants associated with neomorphic sf3b1 mutants.” Shouyoung Peng, Anant A. Agrawal, James Palacino, and Teng Teng are employees of H3 Biomedicine, Inc. Andrew D. Cherniack, Ashton C. Berger, and Galen F. Gao receive research support from Bayer Pharmaceuticals. Gordon B. Mills serves on the External Scientific Review Board of Astrazeneca. Anil Sood is on the Scientific Advisory Board for Kiyatec and is a shareholder in BioPath. Jonathan S. Serody receives funding from Merck, Inc. Kyle R. Covington is an employee of Castle Biosciences, Inc. Preethi H. Gunaratne is founder, CSO, and shareholder of NextmiRNA Therapeutics. Christina Yau is a part-time employee/consultant at NantOmics. Franz X. Schaub is an employee and shareholder of SEngine Precision Medicine, Inc. Carla Grandori is an employee, founder, and shareholder of SEngine Precision Medicine, Inc. Robert N. Eisenman is a member of the Scientific Advisory Boards and shareholder of Shenogen Pharma and Kronos Bio. Daniel J. Weisenberger is a consultant for Zymo Research Corporation. Joshua M. Stuart is the founder of Five3 Genomics and shareholder of NantOmics. Marc T. Goodman receives research support from Merck, Inc. Andrew J. Gentles is a consultant for Cibermed. Charles M. Perou is an equity stock holder, consultant, and Board of Directors member of BioClassifier and GeneCentric Diagnostics and is also listed as an inventor on patent applications on the Breast PAM50 and Lung Cancer Subtyping assays. Matthew Meyerson receives research support from Bayer Pharmaceuticals; is an equity holder in, consultant for, and Scientific Advisory Board chair for OrigiMed; and is an inventor of a patent for EGFR mutation diagnosis in lung cancer, licensed to LabCorp. Eduard Porta-Pardo is an inventor of a patent for domainXplorer. Han Liang is a shareholder and scientific advisor of Precision Scientific and Eagle Nebula. Da Yang is an inventor on a pending patent application describing the use of antisense oligonucleotides against specific lncRNA sequence as diagnostic and therapeutic tools. Yonghong Xiao was an employee and shareholder of TESARO, Inc. Bin Feng is an employee and shareholder of TESARO, Inc. Carter Van Waes received research funding for the study of IAP inhibitor ASTX660 through a Cooperative Agreement between NIDCD, NIH, and Astex Pharmaceuticals. Raunaq Malhotra is an employee and shareholder of Seven Bridges, Inc. Peter W. Laird serves on the Scientific Advisory Board for AnchorDx. Joel Tepper is a consultant at EMD Serono. Kenneth Wang serves on the Advisory Board for Boston Scientific, Microtech, and Olympus. Andrea Califano is a founder, shareholder, and advisory board member of DarwinHealth, Inc. and a shareholder and advisory board member of Tempus, Inc. Toni K. Choueiri serves as needed on advisory boards for Bristol-Myers Squibb, Merck, and Roche. Lawrence Kwong receives research support from Array BioPharma. Sharon E. Plon is a member of the Scientific Advisory Board for Baylor Genetics Laboratory. Beth Y. Karlan serves on the Advisory Board of Invitae.
Published: 2018

2. MS08.02 Induction Therapy for Locally Advanced Thymic Carcinoma

Author: Korst, R., primary
Published: 2019
Full Text: View/download PDF

3. Erratum: The Immune Landscape of Cancer (Immunity (2018) 48(4) (812–830.e14), (S1074761318301213), (10.1016/j.immuni.2018.03.023))

Author: Thorsson, V., Gibbs, D. L., Brown, S. D., Wolf, D., Bortone, D. S., Ou Yang, T. -H., Porta-Pardo, E., Gao, G. F., Plaisier, C. L., Eddy, J. A., Ziv, E., Culhane, A. C., Paull, E. O., Sivakumar, I. K. A., Gentles, A. J., Malhotra, R., Farshidfar, F., Colaprico, A., Parker, J. S., Mose, L. E., N. S., Vo, Liu, J., Liu, Y., Rader, J., Dhankani, V., Reynolds, S. M., Bowlby, R., Califano, A., Cherniack, A. D., Anastassiou, D., Bedognetti, D., Mokrab, Y., Newman, A. M., Rao, A., Chen, K., Krasnitz, A., Hu, H., Malta, T. M., Noushmehr, H., Pedamallu, C. S., Bullman, S., Ojesina, A. I., Lamb, A., Zhou, W., Shen, H., Choueiri, T. K., Weinstein, J. N., Guinney, J., Saltz, J., Holt, R. A., Rabkin, C. S., Caesar-Johnson, S. J., Demchok, J. A., Felau, I., Kasapi, M., Ferguson, M. L., Hutter, C. M., Sofia, H. J., Tarnuzzer, R., Wang, Z., Yang, L., Zenklusen, J. C., Zhang, J. J., Chudamani, S., Lolla, L., Naresh, R., Pihl, T., Sun, Q., Wan, Y., Wu, Y., Cho, J., Defreitas, T., Frazer, S., Gehlenborg, N., Getz, G., Heiman, D. I., Kim, J., Lawrence, M. S., Lin, P., Meier, S., Noble, M. S., Saksena, G., Voet, D., Zhang, H., Bernard, B., Chambwe, N., Knijnenburg, T., Kramer, R., Leinonen, K., Miller, M., Reynolds, S., Shmulevich, I., Zhang, W., Akbani, R., Broom, B. M., Hegde, A. M., Ju, Z., Kanchi, R. S., Korkut, A., Li, J., Liang, H., Ling, S., Liu, W., Lu, Y., Mills, G. B., K. -S., Ng, Ryan, M., Wang, J., Zhang, J., Abeshouse, A., Armenia, J., Chakravarty, D., Chatila, W. K., de Bruijn, I., Gao, J., Gross, B. E., Heins, Z. J., Kundra, R., La, K., Ladanyi, M., Luna, A., Nissan, M. G., Ochoa, A., Phillips, S. M., Reznik, E., Sanchez-Vega, F., Sander, C., Schultz, N., Sheridan, R., Sumer, S. O., Sun, Y., Taylor, B. S., Anur, P., Peto, M., Spellman, P., Benz, C., Stuart, J. M., Wong, C. K., Yau, C., Hayes, D. N., Wilkerson, M. D., Ally, A., Balasundaram, M., Brooks, D., Carlsen, R., Chuah, E., Dhalla, N., Holt, R., Jones, S. J. M., Kasaian, K., Lee, D., Ma, Y., Marra, M. A., Mayo, M., Moore, R. A., Mungall, A. J., Mungall, K., Robertson, A. G., Sadeghi, S., Schein, J. E., Sipahimalani, P., Tam, A., Thiessen, N., Tse, K., Wong, T., Berger, A. C., Beroukhim, R., Cibulskis, C., Gabriel, S. B., Ha, G., Meyerson, M., Schumacher, S. E., Shih, J., Kucherlapati, M. H., Kucherlapati, R. S., Baylin, S., Cope, L., Danilova, L., Bootwalla, M. S., Lai, P. H., Maglinte, D. T., Van Den Berg, D. J., Weisenberger, D. J., Auman, J. T., Balu, S., Bodenheimer, T., Fan, C., Hoadley, K. A., Hoyle, A. P., Jefferys, S. R., Jones, C. D., Meng, S., Mieczkowski, P. A., Perou, A. H., Perou, C. M., Roach, J., Shi, Y., Simons, J. V., Skelly, T., Soloway, M. G., Tan, D., Veluvolu, U., Fan, H., Hinoue, T., Laird, P. W., Bellair, M., Chang, K., Covington, K., Creighton, C. J., Dinh, H., Doddapaneni, H., Donehower, L. A., Drummond, J., Gibbs, R. A., Glenn, R., Hale, W., Han, Y., Hu, J., Korchina, V., Lee, S., Lewis, L., Li, W., Liu, X., Morgan, M., Morton, D., Muzny, D., Santibanez, J., Sheth, M., Shinbrot, E., Wang, L., Wang, M., Wheeler, D. A., Xi, L., Zhao, F., Hess, J., Appelbaum, E. L., Bailey, M., Cordes, M. G., Ding, L., Fronick, C. C., Fulton, L. A., Fulton, R. S., Kandoth, C., Mardis, E. R., Mclellan, M. D., Miller, C. A., Schmidt, H. K., Wilson, R. K., Crain, D., Curley, E., Gardner, J., Lau, K., Mallery, D., Morris, S., Paulauskis, J., Penny, R., Shelton, C., Shelton, T., Sherman, M., Thompson, E., Yena, P., Bowen, J., Gastier-Foster, J. M., Gerken, M., Leraas, K. M., Lichtenberg, T. M., Ramirez, N. C., Wise, L., Zmuda, E., Corcoran, N., Costello, T., Hovens, C., Carvalho, A. L., de Carvalho, A. C., Fregnani, J. H., Longatto-Filho, A., Reis, R. M., Scapulatempo-Neto, C., Silveira, H. C. S., Vidal, D. O., Burnette, A., Eschbacher, J., Hermes, B., Noss, A., Singh, R., Anderson, M. L., Castro, P. D., Ittmann, M., Huntsman, D., Kohl, B., Le, X., Thorp, R., Andry, C., Duffy, E. R., Lyadov, V., Paklina, O., Setdikova, G., Shabunin, A., Tavobilov, M., Mcpherson, C., Warnick, R., Berkowitz, R., Cramer, D., Feltmate, C., Horowitz, N., Kibel, A., Muto, M., Raut, C. P., Malykh, A., Barnholtz-Sloan, J. S., Barrett, W., Devine, K., Fulop, J., Ostrom, Q. T., Shimmel, K., Wolinsky, Y., Sloan, A. E., De Rose, A., Giuliante, F., Goodman, M., Karlan, B. Y., Hagedorn, C. H., Eckman, J., Harr, J., Myers, J., Tucker, K., Zach, L. A., Deyarmin, B., Kvecher, L., Larson, C., Mural, R. J., Somiari, S., Vicha, A., Zelinka, T., Bennett, J., Iacocca, M., Rabeno, B., Swanson, P., Latour, M., Lacombe, L., Tetu, B., Bergeron, A., Mcgraw, M., Staugaitis, S. M., Chabot, J., Hibshoosh, H., Sepulveda, A., Su, T., Wang, T., Potapova, O., Voronina, O., Desjardins, L., Mariani, O., Roman-Roman, S., Sastre, X., Stern, M. -H., Cheng, F., Signoretti, S., Berchuck, A., Bigner, D., Lipp, E., Marks, J., Mccall, S., Mclendon, R., Secord, A., Sharp, A., Behera, M., Brat, D. J., Chen, A., Delman, K., Force, S., Khuri, F., Magliocca, K., Maithel, S., Olson, J. J., Owonikoko, T., Pickens, A., Ramalingam, S., Shin, D. M., Sica, G., Van Meir, E. G., Eijckenboom, W., Gillis, A., Korpershoek, E., Looijenga, L., Oosterhuis, W., Stoop, H., van Kessel, K. E., Zwarthoff, E. C., Calatozzolo, C., Cuppini, L., Cuzzubbo, S., Dimeco, F., Finocchiaro, G., Mattei, L., Perin, A., Pollo, B., Chen, C., Houck, J., Lohavanichbutr, P., Hartmann, A., Stoehr, C., Stoehr, R., Taubert, H., Wach, S., Wullich, B., Kycler, W., Murawa, D., Wiznerowicz, M., Chung, K., Edenfield, W. J., Martin, J., Baudin, E., Bubley, G., Bueno, R., De Rienzo, A., Richards, W. G., Kalkanis, S., Mikkelsen, T., Scarpace, L., Girard, N., Aymerich, M., Campo, E., Gine, E., Guillermo, A. L., Van Bang, N., Hanh, P. T., Phu, B. D., Tang, Y., Colman, H., Evason, K., Dottino, P. R., Martignetti, J. A., Gabra, H., Juhl, H., Akeredolu, T., Stepa, S., Hoon, D., Ahn, K., Kang, K. J., Beuschlein, F., Breggia, A., Birrer, M., Bell, D., Borad, M., Bryce, A. H., Castle, E., Chandan, V., Cheville, J., Copland, J. A., Farnell, M., Flotte, T., Giama, N., Ho, T., Kendrick, M., Kocher, J. -P., Kopp, K., Moser, C., Nagorney, D., O'Brien, D., O'Neill, B. P., Patel, T., Petersen, G., Que, F., Rivera, M., Roberts, L., Smallridge, R., Smyrk, T., Stanton, M., Thompson, R. H., Torbenson, M., Yang, J. D., Zhang, L., Brimo, F., Ajani, J. A., Gonzalez, A. M. A., Behrens, C., Bondaruk, J., Broaddus, R., Czerniak, B., Esmaeli, B., Fujimoto, J., Gershenwald, J., Guo, C., Lazar, A. J., Logothetis, C., Meric-Bernstam, F., Moran, C., Ramondetta, L., Rice, D., Sood, A., Tamboli, P., Thompson, T., Troncoso, P., Tsao, A., Wistuba, I., Carter, C., Haydu, L., Hersey, P., Jakrot, V., Kakavand, H., Kefford, R., Lee, K., Long, G., Mann, G., Quinn, M., Saw, R., Scolyer, R., Shannon, K., Spillane, A., Stretch, O., Synott, M., Thompson, J., Wilmott, J., Al-Ahmadie, H., Chan, T. A., Ghossein, R., Gopalan, A., Levine, D. A., Reuter, V., Singer, S., Singh, B., Tien, N. V., Broudy, T., Mirsaidi, C., Nair, P., Drwiega, P., Miller, J., Smith, J., Zaren, H., Park, J. -W., Hung, N. P., Kebebew, E., Linehan, W. M., Metwalli, A. R., Pacak, K., Pinto, P. A., Schiffman, M., Schmidt, L. S., Vocke, C. D., Wentzensen, N., Worrell, R., Yang, H., Moncrieff, M., Goparaju, C., Melamed, J., Pass, H., Botnariuc, N., Caraman, I., Cernat, M., Chemencedji, I., Clipca, A., Doruc, S., Gorincioi, G., Mura, S., Pirtac, M., Stancul, I., Tcaciuc, D., Albert, M., Alexopoulou, I., Arnaout, A., Bartlett, J., Engel, J., Gilbert, S., Parfitt, J., Sekhon, H., Thomas, G., Rassl, D. M., Rintoul, R. C., Bifulco, C., Tamakawa, R., Urba, W., Hayward, N., Timmers, H., Antenucci, A., Facciolo, F., Grazi, G., Marino, M., Merola, R., de Krijger, R., Gimenez-Roqueplo, A. -P., Piche, A., Chevalier, S., Mckercher, G., Birsoy, K., Barnett, G., Brewer, C., Farver, C., Naska, T., Pennell, N. A., Raymond, D., Schilero, C., Smolenski, K., Williams, F., Morrison, C., Borgia, J. A., Liptay, M. J., Pool, M., Seder, C. W., Junker, K., Omberg, L., Dinkin, M., Manikhas, G., Alvaro, D., Bragazzi, M. C., Cardinale, V., Carpino, G., Gaudio, E., Chesla, D., Cottingham, S., Dubina, M., Moiseenko, F., Dhanasekaran, R., Becker, K. -F., Janssen, K. -P., Slotta-Huspenina, J., Abdel-Rahman, M. H., Aziz, D., Bell, S., Cebulla, C. M., Davis, A., Duell, R., Elder, J. B., Hilty, J., Kumar, B., Lang, J., Lehman, N. L., Mandt, R., Nguyen, P., Pilarski, R., Rai, K., Schoenfield, L., Senecal, K., Wakely, P., Hansen, P., Lechan, R., Powers, J., Tischler, A., Grizzle, W. E., Sexton, K. C., Kastl, A., Henderson, J., Porten, S., Waldmann, J., Fassnacht, M., Asa, S. L., Schadendorf, D., Couce, M., Graefen, M., Huland, H., Sauter, G., Schlomm, T., Simon, R., Tennstedt, P., Olabode, O., Nelson, M., Bathe, O., Carroll, P. R., Chan, J. M., Disaia, P., Glenn, P., Kelley, R. K., Landen, C. N., Phillips, J., Prados, M., Simko, J., Smith-McCune, K., Vandenberg, S., Roggin, K., Fehrenbach, A., Kendler, A., Sifri, S., Steele, R., Jimeno, A., Carey, F., Forgie, I., Mannelli, M., Carney, M., Hernandez, B., Campos, B., Herold-Mende, C., Jungk, C., Unterberg, A., von Deimling, A., Bossler, A., Galbraith, J., Jacobus, L., Knudson, M., Knutson, T., Ma, D., Milhem, M., Sigmund, R., Godwin, A. K., Madan, R., Rosenthal, H. G., Adebamowo, C., Adebamowo, S. N., Boussioutas, A., Beer, D., Giordano, T., Mes-Masson, A. -M., Saad, F., Bocklage, T., Landrum, L., Mannel, R., Moore, K., Moxley, K., Postier, R., Walker, J., Zuna, R., Feldman, M., Valdivieso, F., Dhir, R., Luketich, J., Pinero, E. M. M., Quintero-Aguilo, M., Carlotti, C. G., Dos Santos, J. S., Kemp, R., Sankarankuty, A., Tirapelli, D., Catto, J., Agnew, K., Swisher, E., Creaney, J., Robinson, B., Shelley, C. S., Godwin, E. M., Kendall, S., Shipman, C., Bradford, C., Carey, T., Haddad, A., Moyer, J., Peterson, L., Prince, M., Rozek, L., Wolf, G., Bowman, R., Fong, K. M., Yang, I., Korst, R., Rathmell, W. K., Fantacone-Campbell, J. L., Hooke, J. A., Kovatich, A. J., Shriver, C. D., Dipersio, J., Drake, B., Govindan, R., Heath, S., Ley, T., Van Tine, B., Westervelt, P., Rubin, M. A., Lee, J. I., Aredes, N. D., Mariamidze, A., Serody, J. S., Demicco, E. G., Disis, M. L., and Vincent, B. G.
Subjects: immune, cancer, methods
Published: 2019

4. Preoperative chemotherapy for esophageal cancer with paclitaxel and carboplatin: results of a phase II trial

Author: Keresztes, R S, Port, J L, Pasmantier, M W, Korst, R J, and Altorki, N K
Published: 2003

5. Celecoxib, a Selective Cyclo-Oxygenase-2 Inhibitor, Enhances the Response to Preoperative Paclitaxel and Carboplatin in Early-Stage Non–Small-Cell Lung Cancer

Author: Altorki, N. K., Keresztes, R. S., Port, J. L., Libby, D. M., Korst, R. J., Flieder, D. B., Ferrara, C. A., Yankelevitz, D. F., Subbaramaiah, K., Pasmantier, M. W., and Dannenberg, A. J.
Published: 2003

6. MTE07.02 From Surgical Perspective

Author: Korst, R., primary
Published: 2018
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7. B-002COMPARISON OF SURGICAL APPROACH AND EXTENT OF RESECTION FOR STAGE I AND II THYMIC TUMOURS IN EUROPE, NORTH AMERICA AND ASIA: AN ITMIG RETROSPECTIVE DATABASE GEOGRAPHIC ANALYSIS

Author: Fang, Wentao, primary, Yao, X., additional, Antonicelli, A., additional, Louie, B., additional, Gu, Z., additional, Vallieres, E., additional, Huang, J., additional, Korst, R., additional, and Detterbeck, F., additional
Published: 2016
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8. F-118COMPARISON OF OUTCOMES BETWEEN NEUROENDOCRINE THYMIC TUMOURS AND OTHER SUBTYPES OF THYMIC CARCINOMAS: A JOINT ANALYSIS OF THE EUROPEAN SOCIETY OF THORACIC SURGEONS (ESTS) AND THE INTERNATIONAL THYMIC MALIGNANCY INTEREST GROUP (ITMIG)

Author: Filosso, Pier Luigi, primary, Yao, X., additional, Ahmad, U., additional, Ruffini, E., additional, Antonicelli, A., additional, Huang, J., additional, Guerrera, F., additional, Venuta, F., additional, Van Raemdonck, D., additional, Travis, W., additional, Rimner, A., additional, Thomas, P., additional, Lucchi, M., additional, Rocco, G., additional, Weder, W., additional, Detterbeck, F., additional, and Korst, R., additional
Published: 2015
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9. De invloed van winkelatmosfeer, emoties en betrokkenheid

Author: Korst, R. and Bosmans, A.M.M.
Published: 2010

10. Surgical resection for multifocal (T4 or M1) non-small cell lung cancer (NSCLC): Are the T4 and M1 designations valid?

Author: Port, J. L., primary, Becker, D., additional, Korst, R. J., additional, Lee, P., additional, and Altorki, N. K., additional
Published: 2005
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11. A phase II trial of preoperative paclitaxel/ carboplatin with celecoxib followed by adjuvant celecoxib for esophageal cancer: Preliminary report

Author: Altorki, N. K., primary, Port, J. L., additional, Korst, R. J., additional, and Keresztes, R. S., additional
Published: 2005
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12. Morbidity and mortality for pulmonary resections in lung cancer after induction treatment

Author: Abolhoda, A, primary, Martin, J, additional, Ginsberg, R.J, additional, Rusch, V, additional, Bains, M, additional, Downey, R, additional, Korst, R, additional, Weigel, T, additional, and Kris, M.G, additional
Published: 2000
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13. Extent of resection and lymphadenectomy in early Barrett’s cancer

Author: Korst, R. J., primary and Altorki, N. K., additional
Published: 1997
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14. Lobectomy Improves Ventilatory Function in Selected Patients With Severe COPD

Author: Korst, R. J., Ginsberg, R. J., Ailawadi, M., Bains, M. S., Downey, R. J., Rusch, V. W., and Stover, D.
Published: 1998
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15. Comparison of outcomes between neuroendocrine thymic tumours and other subtypes of thymic carcinomas: a joint analysis of the European Society of Thoracic Surgeons and the International Thymic Malignancy Interest Group

Author: Pl, Filosso, Yao X, Ruffini E, Ahmad U, Antonicelli A, Huang J, Francesco Guerrera, Venuta F, van Raemdonck D, Travis W, Lucchi M, Rimner A, Thomas P, Weder W, Rocco G, Detterbeck F, and Korst R

16. Operative Strategies for Resection of Pulmonary Sarcoma Extending Into the Left Atrium

Author: Korst, R. J. and Rosengart, T. K.
Published: 1999
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17. Distribution of mediastinal lesions across multi-institutional, international, radiology databases

Author: Yan Shen, Edward Z. Sanchez, Guillaume Chassagnon, Demetrius L. Dicks, Anja C. Roden, Marie-Pierre Revel, Giovanella Palmieri, Nicolas Girard, Wentao Fang, Ami N. Rubinowitz, Sarah M. Jenkins, Brett W. Carter, Robert J. Korst, Darin White, Conrad Falkson, Edith M. Marom, Samantha Sigurdson, Mattia Di Segni, Silvana Del Vecchio, Eyal Klang, Engjellush Shumeri, Margaret Ottaviano, Mirella Marino, Jane P. Ko, Grant M. Spears, Julian R. Molina, Sabrina Segreto, Jeanne B. Ackman, Frank C. Detterbeck, Roden, Ac, Fang, W, Shen, Y, Carter, Bw, White, Db, Jenkins, Sm, Spears, Gm, Molina, Jr, Klang, E, Segni, Md, Ackman, Jb, Sanchez, Ez, Girard, N, Shumeri, E, Revel M., -P, Chassagnon, G, Rubinowitz, A, Dicks, D, Detterbeck, F, Ko J., P, Falkson, Cb, Sigurdson, S, Segreto, S, Del Vecchio, S, Palmieri, G, Ottaviano, M, Marino, M, Korst, R, and Marom, Em
Subjects: 0301 basic medicine, Pulmonary and Respiratory Medicine, China, medicine.medical_specialty, Lung Neoplasms, computer.software_genre, Mediastinal Neoplasms, Lesion, 03 medical and health sciences, 0302 clinical medicine, Biopsy, medicine, Humans, Retrospective Studies, Database, medicine.diagnostic_test, business.industry, Mediastinum, Retrospective cohort study, Nodule (medicine), Magnetic resonance imaging, Thymus Neoplasms, Europe, 030104 developmental biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Radiology, Differential diagnosis, medicine.symptom, business, Mediastinal Cyst, computer
Abstract: Mediastinal lesions are uncommon; studies on their distribution are, in general, small and from a single institution. Furthermore, these studies are usually based on pathology or surgical databases and, therefore, miss many lesions that did not undergo biopsy or resection. Our aim was to identify the distribution of lesions in the mediastinum in a large international, multi-institutional cohort.At each participating institution, a standardized retrospective radiology database search was performed for interpretations of computed tomography, positron emission tomography-computed tomography, and magnetic resonance imaging scans including any of the following terms: "mediastinal nodule," "mediastinal lesion," "mediastinal mass," or "mediastinal abnormality" (2011-2014). Standardized data were collected. Statistical analysis was performed.Among 3308 cases, thymomas (27.8%), benign mediastinal cysts (20.0%), and lymphomas (16.1%) were most common. The distribution of lesions varied among mediastinal compartments; thymomas (38.3%), benign cysts (16.8%), and neurogenic tumors (53.9%) were the most common lesions in the prevascular, visceral, and paravertebral mediastinum, respectively (p0.001). Mediastinal compartment was associated with age; patients with paravertebral lesions were the youngest (p0.0001). Mediastinal lesions differed by continent or country, with benign cysts being the most common mediastinal lesions in the People's Republic of China, thymomas in Europe, and lymphomas in North America and Israel (p0.001). Benign cysts, thymic carcinomas, and metastases were more often seen in larger hospitals, whereas lymphomas and thymic hyperplasia occurred more often in smaller hospitals (p 0.01).Our study confirmed that the spectrum and frequency of mediastinal lesions depend on mediastinal compartment and age. This information provides helpful demographic data and is important when considering the differential diagnosis of a mediastinal lesion.
Published: 2020

18. Machine Learning Detects Pan-cancer Ras Pathway Activation in The Cancer Genome Atlas

Author: Gregory P. Way, Francisco Sanchez-Vega, Konnor La, Joshua Armenia, Walid K. Chatila, Augustin Luna, Chris Sander, Andrew D. Cherniack, Marco Mina, Giovanni Ciriello, Nikolaus Schultz, Yolanda Sanchez, Casey S. Greene, Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, Gad Getz, David I. Heiman, Jaegil Kim, Michael S. Lawrence, Pei Lin, Sam Meier, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Yuexin Liu, Michael Miller, Sheila Reynolds, Ilya Shmulevich, Vesteinn Thorsson, Wei Zhang, Rehan Akbani, Bradley M. Broom, Apurva M. Hegde, Zhenlin Ju, Rupa S. Kanchi, Anil Korkut, Jun Li, Han Liang, Shiyun Ling, Wenbin Liu, Yiling Lu, Gordon B. Mills, Kwok-Shing Ng, Arvind Rao, Michael Ryan, Jing Wang, John N. Weinstein, Jiexin Zhang, Adam Abeshouse, Debyani Chakravarty, Ino de Bruijn, Jianjiong Gao, Benjamin E. Gross, Zachary J. Heins, Ritika Kundra, Marc Ladanyi, Moriah G. Nissan, Angelica Ochoa, Sarah M. Phillips, Ed Reznik, Robert Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, Joshua M. Stuart, Christopher K. Wong, Christina Yau, D. Neil Hayes, Joel S. Parker, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, A. Gordon Robertson, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Ashton C. Berger, Rameen Beroukhim, Carrie Cibulskis, Stacey B. Gabriel, Galen F. Gao, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju S. Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz S. Bootwalla, Phillip H. Lai, Dennis T. Maglinte, David J. Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Cheng Fan, Katherine A. Hoadley, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Amy H. Perou, Charles M. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Huihui Fan, Toshinori Hinoue, Peter W. Laird, Hui Shen, Wanding Zhou, Michelle Bellair, Kyle Chang, Kyle Covington, Chad J. Creighton, Huyen Dinh, HarshaVardhan Doddapaneni, Lawrence A. Donehower, Jennifer Drummond, Richard A. Gibbs, Robert Glenn, Walker Hale, Yi Han, Jianhong Hu, Viktoriya Korchina, Sandra Lee, Lora Lewis, Wei Li, Xiuping Liu, Margaret Morgan, Donna Morton, Donna Muzny, Jireh Santibanez, Margi Sheth, Eve Shinbrot, Linghua Wang, Min Wang, David A. Wheeler, Liu Xi, Fengmei Zhao, Julian Hess, Elizabeth L. Appelbaum, Matthew Bailey, Matthew G. Cordes, Li Ding, Catrina C. Fronick, Lucinda A. Fulton, Robert S. Fulton, Cyriac Kandoth, Elaine R. Mardis, Michael D. McLellan, Christopher A. Miller, Heather K. Schmidt, Richard K. Wilson, Daniel Crain, Erin Curley, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Mark Sherman, Eric Thompson, Peggy Yena, Jay Bowen, Julie M. Gastier-Foster, Mark Gerken, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Niall Corcoran, Tony Costello, Christopher Hovens, Andre L. Carvalho, Ana C. de Carvalho, José H. Fregnani, Adhemar Longatto-Filho, Rui M. Reis, Cristovam Scapulatempo-Neto, Henrique C.S. Silveira, Daniel O. Vidal, Andrew Burnette, Jennifer Eschbacher, Beth Hermes, Ardene Noss, Rosy Singh, Matthew L. Anderson, Patricia D. Castro, Michael Ittmann, David Huntsman, Bernard Kohl, Xuan Le, Richard Thorp, Chris Andry, Elizabeth R. Duffy, Vladimir Lyadov, Oxana Paklina, Galiya Setdikova, Alexey Shabunin, Mikhail Tavobilov, Christopher McPherson, Ronald Warnick, Ross Berkowitz, Daniel Cramer, Colleen Feltmate, Neil Horowitz, Adam Kibel, Michael Muto, Chandrajit P. Raut, Andrei Malykh, Jill S. Barnholtz-Sloan, Wendi Barrett, Karen Devine, Jordonna Fulop, Quinn T. Ostrom, Kristen Shimmel, Yingli Wolinsky, Andrew E. Sloan, Agostino De Rose, Felice Giuliante, Marc Goodman, Beth Y. Karlan, Curt H. Hagedorn, John Eckman, Jodi Harr, Jerome Myers, Kelinda Tucker, Leigh Anne Zach, Brenda Deyarmin, Hai Hu, Leonid Kvecher, Caroline Larson, Richard J. Mural, Stella Somiari, Ales Vicha, Tomas Zelinka, Joseph Bennett, Mary Iacocca, Brenda Rabeno, Patricia Swanson, Mathieu Latour, Louis Lacombe, Bernard Têtu, Alain Bergeron, Mary McGraw, Susan M. Staugaitis, John Chabot, Hanina Hibshoosh, Antonia Sepulveda, Tao Su, Timothy Wang, Olga Potapova, Olga Voronina, Laurence Desjardins, Odette Mariani, Sergio Roman-Roman, Xavier Sastre, Marc-Henri Stern, Feixiong Cheng, Sabina Signoretti, Andrew Berchuck, Darell Bigner, Eric Lipp, Jeffrey Marks, Shannon McCall, Roger McLendon, Angeles Secord, Alexis Sharp, Madhusmita Behera, Daniel J. Brat, Amy Chen, Keith Delman, Seth Force, Fadlo Khuri, Kelly Magliocca, Shishir Maithel, Jeffrey J. Olson, Taofeek Owonikoko, Alan Pickens, Suresh Ramalingam, Dong M. Shin, Gabriel Sica, Erwin G. Van Meir, Hongzheng Zhang, Wil Eijckenboom, Ad Gillis, Esther Korpershoek, Leendert Looijenga, Wolter Oosterhuis, Hans Stoop, Kim E. van Kessel, Ellen C. 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Subjects: 0301 basic medicine, Neuroblastoma RAS viral oncogene homolog, Genetics and Molecular Biology (all), PATHOGENESIS, pan-cancer, PROTEIN, Cancer Genome Atlas Research Network, medicine.disease_cause, computer.software_genre, Genome, Biochemistry, Transcriptome, Gene expression, HRAS, KRAS, NF1, NRAS, Ras, TCGA, drug sensitivity, machine learning, Neoplasms, PRECISION ONCOLOGY, lcsh:QH301-705.5, Regulation of gene expression, PREVIOUSLY TREATED PATIENTS, 3. Good health, Gene Expression Regulation, Neoplastic, PHASE-II, Life Sciences & Biomedicine, Signal Transduction, Biology, Machine learning, General Biochemistry, Genetics and Molecular Biology, Article, BRAF, 03 medical and health sciences, Cell Line, Tumor, medicine, Biochemistry, Genetics and Molecular Biology (all), Humans, Gene, SIGNATURES, Science & Technology, business.industry, Genome, Human, MUTATIONS, EXPRESSÃO GÊNICA, Cell Biology, SELUMETINIB, GENE, 030104 developmental biology, lcsh:Biology (General), Selumetinib, ras Proteins, Artificial intelligence, business, computer
Abstract: SUMMARY Precision oncology uses genomic evidence to match patients with treatment but often fails to identify all patients who may respond. The transcriptome of these “hidden responders” may reveal responsive molecular states. We describe and evaluate a machine-learning approach to classify aberrant pathway activity in tumors, which may aid in hidden responder identification. The algorithm integrates RNA-seq, copy number, and mutations from 33 different cancer types across The Cancer Genome Atlas (TCGA) PanCanAtlas project to predict aberrant molecular states in tumors. Applied to the Ras pathway, the method detects Ras activation across cancer types and identifies phenocopying variants. The model, trained on human tumors, can predict response to MEK inhibitors in wild-type Ras cell lines. We also present data that suggest that multiple hits in the Ras pathway confer increased Ras activity. The transcriptome is underused in precision oncology and, combined with machine learning, can aid in the identification of hidden responders., In Brief Way et al. develop a machine-learning approach using PanCanAtlas data to detect Ras activation in cancer. Integrating mutation, copy number, and expression data, the authors show that their method detects Ras-activating variants in tumors and sensitivity to MEK inhibitors in cell lines.
Published: 2018

19. A Pan-Cancer Analysis of Enhancer Expression in Nearly 9000 Patient Samples

Author: Han Chen, Chunyan Li, Xinxin Peng, Zhicheng Zhou, John N. Weinstein, Han Liang, Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, Gad Getz, David I. Heiman, Jaegil Kim, Michael S. Lawrence, Pei Lin, Sam Meier, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Yuexin Liu, Michael Miller, Sheila Reynolds, Ilya Shmulevich, Vesteinn Thorsson, Wei Zhang, Rehan Akbani, Bradley M. Broom, Apurva M. Hegde, Zhenlin Ju, Rupa S. Kanchi, Anil Korkut, Jun Li, Shiyun Ling, Wenbin Liu, Yiling Lu, Gordon B. Mills, Kwok-Shing Ng, Arvind Rao, Michael Ryan, Jing Wang, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K. Chatila, Ino de Bruijn, Jianjiong Gao, Benjamin E. Gross, Zachary J. Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G. Nissan, Angelica Ochoa, Sarah M. Phillips, Ed Reznik, Francisco Sanchez-Vega, Chris Sander, Nikolaus Schultz, Robert Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, Joshua M. Stuart, Christopher K. Wong, Christina Yau, D. Neil Hayes, Joel S. Parker, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, A. Gordon Robertson, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Ashton C. Berger, Rameen Beroukhim, Andrew D. Cherniack, Carrie Cibulskis, Stacey B. Gabriel, Galen F. Gao, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju S. Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz S. Bootwalla, Phillip H. Lai, Dennis T. Maglinte, David J. Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Cheng Fan, Katherine A. Hoadley, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Amy H. Perou, Charles M. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Huihui Fan, Toshinori Hinoue, Peter W. Laird, Hui Shen, Wanding Zhou, Michelle Bellair, Kyle Chang, Kyle Covington, Chad J. Creighton, Huyen Dinh, HarshaVardhan Doddapaneni, Lawrence A. Donehower, Jennifer Drummond, Richard A. Gibbs, Robert Glenn, Walker Hale, Yi Han, Jianhong Hu, Viktoriya Korchina, Sandra Lee, Lora Lewis, Wei Li, Xiuping Liu, Margaret Morgan, Donna Morton, Donna Muzny, Jireh Santibanez, Margi Sheth, Eve Shinbrot, Linghua Wang, Min Wang, David A. Wheeler, Liu Xi, Fengmei Zhao, Julian Hess, Elizabeth L. Appelbaum, Matthew Bailey, Matthew G. Cordes, Li Ding, Catrina C. Fronick, Lucinda A. Fulton, Robert S. Fulton, Cyriac Kandoth, Elaine R. Mardis, Michael D. McLellan, Christopher A. Miller, Heather K. Schmidt, Richard K. Wilson, Daniel Crain, Erin Curley, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Mark Sherman, Eric Thompson, Peggy Yena, Jay Bowen, Julie M. Gastier-Foster, Mark Gerken, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Niall Corcoran, Tony Costello, Christopher Hovens, Andre L. Carvalho, Ana C. de Carvalho, José H. Fregnani, Adhemar Longatto-Filho, Rui M. Reis, Cristovam Scapulatempo-Neto, Henrique C.S. Silveira, Daniel O. Vidal, Andrew Burnette, Jennifer Eschbacher, Beth Hermes, Ardene Noss, Rosy Singh, Matthew L. Anderson, Patricia D. Castro, Michael Ittmann, David Huntsman, Bernard Kohl, Xuan Le, Richard Thorp, Chris Andry, Elizabeth R. Duffy, Vladimir Lyadov, Oxana Paklina, Galiya Setdikova, Alexey Shabunin, Mikhail Tavobilov, Christopher McPherson, Ronald Warnick, Ross Berkowitz, Daniel Cramer, Colleen Feltmate, Neil Horowitz, Adam Kibel, Michael Muto, Chandrajit P. Raut, Andrei Malykh, Jill S. Barnholtz-Sloan, Wendi Barrett, Karen Devine, Jordonna Fulop, Quinn T. Ostrom, Kristen Shimmel, Yingli Wolinsky, Andrew E. Sloan, Agostino De Rose, Felice Giuliante, Marc Goodman, Beth Y. Karlan, Curt H. Hagedorn, John Eckman, Jodi Harr, Jerome Myers, Kelinda Tucker, Leigh Anne Zach, Brenda Deyarmin, Hai Hu, Leonid Kvecher, Caroline Larson, Richard J. Mural, Stella Somiari, Ales Vicha, Tomas Zelinka, Joseph Bennett, Mary Iacocca, Brenda Rabeno, Patricia Swanson, Mathieu Latour, Louis Lacombe, Bernard Têtu, Alain Bergeron, Mary McGraw, Susan M. Staugaitis, John Chabot, Hanina Hibshoosh, Antonia Sepulveda, Tao Su, Timothy Wang, Olga Potapova, Olga Voronina, Laurence Desjardins, Odette Mariani, Sergio Roman-Roman, Xavier Sastre, Marc-Henri Stern, Feixiong Cheng, Sabina Signoretti, Andrew Berchuck, Darell Bigner, Eric Lipp, Jeffrey Marks, Shannon McCall, Roger McLendon, Angeles Secord, Alexis Sharp, Madhusmita Behera, Daniel J. Brat, Amy Chen, Keith Delman, Seth Force, Fadlo Khuri, Kelly Magliocca, Shishir Maithel, Jeffrey J. Olson, Taofeek Owonikoko, Alan Pickens, Suresh Ramalingam, Dong M. Shin, Gabriel Sica, Erwin G. Van Meir, Hongzheng Zhang, Wil Eijckenboom, Ad Gillis, Esther Korpershoek, Leendert Looijenga, Wolter Oosterhuis, Hans Stoop, Kim E. van Kessel, Ellen C. Zwarthoff, Chiara Calatozzolo, Lucia Cuppini, Stefania Cuzzubbo, Francesco DiMeco, Gaetano Finocchiaro, Luca Mattei, Alessandro Perin, Bianca Pollo, Chu Chen, John Houck, Pawadee Lohavanichbutr, Arndt Hartmann, Christine Stoehr, Robert Stoehr, Helge Taubert, Sven Wach, Bernd Wullich, Witold Kycler, Dawid Murawa, Maciej Wiznerowicz, Ki Chung, W. Jeffrey Edenfield, Julie Martin, Eric Baudin, Glenn Bubley, Raphael Bueno, Assunta De Rienzo, William G. Richards, Steven Kalkanis, Tom Mikkelsen, Houtan Noushmehr, Lisa Scarpace, Nicolas Girard, Marta Aymerich, Elias Campo, Eva Giné, Armando López Guillermo, Nguyen Van Bang, Phan Thi Hanh, Bui Duc Phu, Yufang Tang, Howard Colman, Kimberley Evason, Peter R. Dottino, John A. Martignetti, Hani Gabra, Hartmut Juhl, Teniola Akeredolu, Serghei Stepa, Dave Hoon, Keunsoo Ahn, Koo Jeong Kang, Felix Beuschlein, Anne Breggia, Michael Birrer, Debra Bell, Mitesh Borad, Alan H. Bryce, Erik Castle, Vishal Chandan, John Cheville, John A. Copland, Michael Farnell, Thomas Flotte, Nasra Giama, Thai Ho, Michael Kendrick, Jean-Pierre Kocher, Karla Kopp, Catherine Moser, David Nagorney, Daniel O’Brien, Brian Patrick O’Neill, Tushar Patel, Gloria Petersen, Florencia Que, Michael Rivera, Lewis Roberts, Robert Smallridge, Thomas Smyrk, Melissa Stanton, R. Houston Thompson, Michael Torbenson, Ju Dong Yang, Lizhi Zhang, Fadi Brimo, Jaffer A. Ajani, Ana Maria Angulo Gonzalez, Carmen Behrens, Jolanta Bondaruk, Russell Broaddus, Bogdan Czerniak, Bita Esmaeli, Junya Fujimoto, Jeffrey Gershenwald, Charles Guo, Alexander J. Lazar, Christopher Logothetis, Funda Meric-Bernstam, Cesar Moran, Lois Ramondetta, David Rice, Anil Sood, Pheroze Tamboli, Timothy Thompson, Patricia Troncoso, Anne Tsao, Ignacio Wistuba, Candace Carter, Lauren Haydu, Peter Hersey, Valerie Jakrot, Hojabr Kakavand, Richard Kefford, Kenneth Lee, Georgina Long, Graham Mann, Michael Quinn, Robyn Saw, Richard Scolyer, Kerwin Shannon, Andrew Spillane, Jonathan Stretch, Maria Synott, John Thompson, James Wilmott, Hikmat Al-Ahmadie, Timothy A. Chan, Ronald Ghossein, Anuradha Gopalan, Douglas A. Levine, Victor Reuter, Samuel Singer, Bhuvanesh Singh, Nguyen Viet Tien, Thomas Broudy, Cyrus Mirsaidi, Praveen Nair, Paul Drwiega, Judy Miller, Jennifer Smith, Howard Zaren, Joong-Won Park, Nguyen Phi Hung, Electron Kebebew, W. Marston Linehan, Adam R. Metwalli, Karel Pacak, Peter A. Pinto, Mark Schiffman, Laura S. Schmidt, Cathy D. Vocke, Nicolas Wentzensen, Robert Worrell, Hannah Yang, Marc Moncrieff, Chandra Goparaju, Jonathan Melamed, Harvey Pass, Natalia Botnariuc, Irina Caraman, Mircea Cernat, Inga Chemencedji, Adrian Clipca, Serghei Doruc, Ghenadie Gorincioi, Sergiu Mura, Maria Pirtac, Irina Stancul, Diana Tcaciuc, Monique Albert, Iakovina Alexopoulou, Angel Arnaout, John Bartlett, Jay Engel, Sebastien Gilbert, Jeremy Parfitt, Harman Sekhon, George Thomas, Doris M. Rassl, Robert C. Rintoul, Carlo Bifulco, Raina Tamakawa, Walter Urba, Nicholas Hayward, Henri Timmers, Anna Antenucci, Francesco Facciolo, Gianluca Grazi, Mirella Marino, Roberta Merola, Ronald de Krijger, Anne-Paule Gimenez-Roqueplo, Alain Piché, Simone Chevalier, Ginette McKercher, Kivanc Birsoy, Gene Barnett, Cathy Brewer, Carol Farver, Theresa Naska, Nathan A. Pennell, Daniel Raymond, Cathy Schilero, Kathy Smolenski, Felicia Williams, Carl Morrison, Jeffrey A. Borgia, Michael J. Liptay, Mark Pool, Christopher W. Seder, Kerstin Junker, Larsson Omberg, Mikhail Dinkin, George Manikhas, Domenico Alvaro, Maria Consiglia Bragazzi, Vincenzo Cardinale, Guido Carpino, Eugenio Gaudio, David Chesla, Sandra Cottingham, Michael Dubina, Fedor Moiseenko, Renumathy Dhanasekaran, Karl-Friedrich Becker, Klaus-Peter Janssen, Julia Slotta-Huspenina, Mohamed H. Abdel-Rahman, Dina Aziz, Sue Bell, Colleen M. Cebulla, Amy Davis, Rebecca Duell, J. Bradley Elder, Joe Hilty, Bahavna Kumar, James Lang, Norman L. Lehman, Randy Mandt, Phuong Nguyen, Robert Pilarski, Karan Rai, Lynn Schoenfield, Kelly Senecal, Paul Wakely, Paul Hansen, Ronald Lechan, James Powers, Arthur Tischler, William E. Grizzle, Katherine C. Sexton, Alison Kastl, Joel Henderson, Sima Porten, Jens Waldmann, Martin Fassnacht, Sylvia L. Asa, Dirk Schadendorf, Marta Couce, Markus Graefen, Hartwig Huland, Guido Sauter, Thorsten Schlomm, Ronald Simon, Pierre Tennstedt, Oluwole Olabode, Mark Nelson, Oliver Bathe, Peter R. Carroll, June M. Chan, Philip Disaia, Pat Glenn, Robin K. Kelley, Charles N. Landen, Joanna Phillips, Michael Prados, Jeffry Simko, Karen Smith-McCune, Scott VandenBerg, Kevin Roggin, Ashley Fehrenbach, Ady Kendler, Suzanne Sifri, Ruth Steele, Antonio Jimeno, Francis Carey, Ian Forgie, Massimo Mannelli, Michael Carney, Brenda Hernandez, Benito Campos, Christel Herold-Mende, Christin Jungk, Andreas Unterberg, Andreas von Deimling, Aaron Bossler, Joseph Galbraith, Laura Jacobus, Michael Knudson, Tina Knutson, Deqin Ma, Mohammed Milhem, Rita Sigmund, Andrew K. Godwin, Rashna Madan, Howard G. Rosenthal, Clement Adebamowo, Sally N. Adebamowo, Alex Boussioutas, David Beer, Thomas Giordano, Anne-Marie Mes-Masson, Fred Saad, Therese Bocklage, Lisa Landrum, Robert Mannel, Kathleen Moore, Katherine Moxley, Russel Postier, Joan Walker, Rosemary Zuna, Michael Feldman, Federico Valdivieso, Rajiv Dhir, James Luketich, Edna M. Mora Pinero, Mario Quintero-Aguilo, Carlos Gilberto Carlotti, Jose Sebastião Dos Santos, Rafael Kemp, Ajith Sankarankuty, Daniela Tirapelli, James Catto, Kathy Agnew, Elizabeth Swisher, Jenette Creaney, Bruce Robinson, Carl Simon Shelley, Eryn M. Godwin, Sara Kendall, Cassaundra Shipman, Carol Bradford, Thomas Carey, Andrea Haddad, Jeffey Moyer, Lisa Peterson, Mark Prince, Laura Rozek, Gregory Wolf, Rayleen Bowman, Kwun M. Fong, Ian Yang, Robert Korst, W. Kimryn Rathmell, J. Leigh Fantacone-Campbell, Jeffrey A. Hooke, Albert J. Kovatich, Craig D. Shriver, John DiPersio, Bettina Drake, Ramaswamy Govindan, Sharon Heath, Timothy Ley, Brian Van Tine, Peter Westervelt, Mark A. Rubin, Jung Il Lee, Natália D. Aredes, Armaz Mariamidze, Chen H., Li C., Peng X., Zhou Z., Weinstein J.N., Caesar-Johnson S.J., Demchok J.A., Felau I., Kasapi M., Ferguson M.L., Hutter C.M., Sofia H.J., Tarnuzzer R., Wang Z., Yang L., Zenklusen J.C., Zhang J.J., Chudamani S., Liu J., Lolla L., Naresh R., Pihl T., Sun Q., Wan Y., Wu Y., Cho J., DeFreitas T., Frazer S., Gehlenborg N., Getz G., Heiman D.I., Kim J., Lawrence M.S., Lin P., Meier S., Noble M.S., Saksena G., Voet D., Zhang H., Bernard B., Chambwe N., Dhankani V., Knijnenburg T., Kramer R., Leinonen K., Liu Y., Miller M., Reynolds S., Shmulevich I., Thorsson V., Zhang W., Akbani R., Broom B.M., Hegde A.M., Ju Z., Kanchi R.S., Korkut A., Li J., Liang H., Ling S., Liu W., Lu Y., Mills G.B., Ng K.-S., Rao A., Ryan M., Wang J., Zhang J., Abeshouse A., Armenia J., Chakravarty D., Chatila W.K., de Bruijn I., Gao J., Gross B.E., Heins Z.J., Kundra R., La K., Ladanyi M., Luna A., Nissan M.G., Ochoa A., Phillips S.M., Reznik E., Sanchez-Vega F., Sander C., Schultz N., Sheridan R., Sumer S.O., Sun Y., Taylor B.S., Anur P., Peto M., Spellman P., Benz C., Stuart J.M., Wong C.K., Yau C., Hayes D.N., Parker J.S., Wilkerson M.D., Ally A., Balasundaram M., Bowlby R., Brooks D., Carlsen R., Chuah E., Dhalla N., Holt R., Jones S.J.M., Kasaian K., Lee D., Ma Y., Marra M.A., Mayo M., Moore R.A., Mungall A.J., Mungall K., Robertson A.G., Sadeghi S., Schein J.E., Sipahimalani P., Tam A., Thiessen N., Tse K., Wong T., Berger A.C., Beroukhim R., Cherniack A.D., Cibulskis C., Gabriel S.B., Gao G.F., Ha G., Meyerson M., Schumacher S.E., Shih J., Kucherlapati M.H., Kucherlapati R.S., Baylin S., Cope L., Danilova L., Bootwalla M.S., Lai P.H., Maglinte D.T., Van Den Berg D.J., Weisenberger D.J., Auman J.T., Balu S., Bodenheimer T., Fan C., Hoadley K.A., Hoyle A.P., Jefferys S.R., Jones C.D., Meng S., Mieczkowski P.A., Mose L.E., Perou A.H., Perou C.M., Roach J., Shi Y., Simons J.V., Skelly T., Soloway M.G., Tan D., Veluvolu U., Fan H., Hinoue T., Laird P.W., Shen H., Zhou W., Bellair M., Chang K., Covington K., Creighton C.J., Dinh H., Doddapaneni H., Donehower L.A., Drummond J., Gibbs R.A., Glenn R., Hale W., Han Y., Hu J., Korchina V., Lee S., Lewis L., Li W., Liu X., Morgan M., Morton D., Muzny D., Santibanez J., Sheth M., Shinbrot E., Wang L., Wang M., Wheeler D.A., Xi L., Zhao F., Hess J., Appelbaum E.L., Bailey M., Cordes M.G., Ding L., Fronick C.C., Fulton L.A., Fulton R.S., Kandoth C., Mardis E.R., McLellan M.D., Miller C.A., Schmidt H.K., Wilson R.K., Crain D., Curley E., Gardner J., Lau K., Mallery D., Morris S., Paulauskis J., Penny R., Shelton C., Shelton T., Sherman M., Thompson E., Yena P., Bowen J., Gastier-Foster J.M., Gerken M., Leraas K.M., Lichtenberg T.M., Ramirez N.C., Wise L., Zmuda E., Corcoran N., Costello T., Hovens C., Carvalho A.L., de Carvalho A.C., Fregnani J.H., Longatto-Filho A., Reis R.M., Scapulatempo-Neto C., Silveira H.C.S., Vidal D.O., Burnette A., Eschbacher J., Hermes B., Noss A., Singh R., Anderson M.L., Castro P.D., Ittmann M., Huntsman D., Kohl B., Le X., Thorp R., Andry C., Duffy E.R., Lyadov V., Paklina O., Setdikova G., Shabunin A., Tavobilov M., McPherson C., Warnick R., Berkowitz R., Cramer D., Feltmate C., Horowitz N., Kibel A., Muto M., Raut C.P., Malykh A., Barnholtz-Sloan J.S., Barrett W., Devine K., Fulop J., Ostrom Q.T., Shimmel K., Wolinsky Y., Sloan A.E., De Rose A., Giuliante F., Goodman M., Karlan B.Y., Hagedorn C.H., Eckman J., Harr J., Myers J., Tucker K., Zach L.A., Deyarmin B., Hu H., Kvecher L., Larson C., Mural R.J., Somiari S., Vicha A., Zelinka T., Bennett J., Iacocca M., Rabeno B., Swanson P., Latour M., Lacombe L., Tetu B., Bergeron A., McGraw M., Staugaitis S.M., Chabot J., Hibshoosh H., Sepulveda A., Su T., Wang T., Potapova O., Voronina O., Desjardins L., Mariani O., Roman-Roman S., Sastre X., Stern M.-H., Cheng F., Signoretti S., Berchuck A., Bigner D., Lipp E., Marks J., McCall S., McLendon R., Secord A., Sharp A., Behera M., Brat D.J., Chen A., Delman K., Force S., Khuri F., Magliocca K., Maithel S., Olson J.J., Owonikoko T., Pickens A., Ramalingam S., Shin D.M., Sica G., Van Meir E.G., Eijckenboom W., Gillis A., Korpershoek E., Looijenga L., Oosterhuis W., Stoop H., van Kessel K.E., Zwarthoff E.C., Calatozzolo C., Cuppini L., Cuzzubbo S., DiMeco F., Finocchiaro G., Mattei L., Perin A., Pollo B., Chen C., Houck J., Lohavanichbutr P., Hartmann A., Stoehr C., Stoehr R., Taubert H., Wach S., Wullich B., Kycler W., Murawa D., Wiznerowicz M., Chung K., Edenfield W.J., Martin J., Baudin E., Bubley G., Bueno R., De Rienzo A., Richards W.G., Kalkanis S., Mikkelsen T., Noushmehr H., Scarpace L., Girard N., Aymerich M., Campo E., Gine E., Guillermo A.L., Van Bang N., Hanh P.T., Phu B.D., Tang Y., Colman H., Evason K., Dottino P.R., Martignetti J.A., Gabra H., Juhl H., Akeredolu T., Stepa S., Hoon D., Ahn K., Kang K.J., Beuschlein F., Breggia A., Birrer M., Bell D., Borad M., Bryce A.H., Castle E., Chandan V., Cheville J., Copland J.A., Farnell M., Flotte T., Giama N., Ho T., Kendrick M., Kocher J.-P., Kopp K., Moser C., Nagorney D., O'Brien D., O'Neill B.P., Patel T., Petersen G., Que F., Rivera M., Roberts L., Smallridge R., Smyrk T., Stanton M., Thompson R.H., Torbenson M., Yang J.D., Zhang L., Brimo F., Ajani J.A., Gonzalez A.M.A., Behrens C., Bondaruk J., Broaddus R., Czerniak B., Esmaeli B., Fujimoto J., Gershenwald J., Guo C., Lazar A.J., Logothetis C., Meric-Bernstam F., Moran C., Ramondetta L., Rice D., Sood A., Tamboli P., Thompson T., Troncoso P., Tsao A., Wistuba I., Carter C., Haydu L., Hersey P., Jakrot V., Kakavand H., Kefford R., Lee K., Long G., Mann G., Quinn M., Saw R., Scolyer R., Shannon K., Spillane A., Stretch J., Synott M., Thompson J., Wilmott J., Al-Ahmadie H., Chan T.A., Ghossein R., Gopalan A., Levine D.A., Reuter V., Singer S., Singh B., Tien N.V., Broudy T., Mirsaidi C., Nair P., Drwiega P., Miller J., Smith J., Zaren H., Park J.-W., Hung N.P., Kebebew E., Linehan W.M., Metwalli A.R., Pacak K., Pinto P.A., Schiffman M., Schmidt L.S., Vocke C.D., Wentzensen N., Worrell R., Yang H., Moncrieff M., Goparaju C., Melamed J., Pass H., Botnariuc N., Caraman I., Cernat M., Chemencedji I., Clipca A., Doruc S., Gorincioi G., Mura S., Pirtac M., Stancul I., Tcaciuc D., Albert M., Alexopoulou I., Arnaout A., Bartlett J., Engel J., Gilbert S., Parfitt J., Sekhon H., Thomas G., Rassl D.M., Rintoul R.C., Bifulco C., Tamakawa R., Urba W., Hayward N., Timmers H., Antenucci A., Facciolo F., Grazi G., Marino M., Merola R., de Krijger R., Gimenez-Roqueplo A.-P., Piche A., Chevalier S., McKercher G., Birsoy K., Barnett G., Brewer C., Farver C., Naska T., Pennell N.A., Raymond D., Schilero C., Smolenski K., Williams F., Morrison C., Borgia J.A., Liptay M.J., Pool M., Seder C.W., Junker K., Omberg L., Dinkin M., Manikhas G., Alvaro D., Bragazzi M.C., Cardinale V., Carpino G., Gaudio E., Chesla D., Cottingham S., Dubina M., Moiseenko F., Dhanasekaran R., Becker K.-F., Janssen K.-P., Slotta-Huspenina J., Abdel-Rahman M.H., Aziz D., Bell S., Cebulla C.M., Davis A., Duell R., Elder J.B., Hilty J., Kumar B., Lang J., Lehman N.L., Mandt R., Nguyen P., Pilarski R., Rai K., Schoenfield L., Senecal K., Wakely P., Hansen P., Lechan R., Powers J., Tischler A., Grizzle W.E., Sexton K.C., Kastl A., Henderson J., Porten S., Waldmann J., Fassnacht M., Asa S.L., Schadendorf D., Couce M., Graefen M., Huland H., Sauter G., Schlomm T., Simon R., Tennstedt P., Olabode O., Nelson M., Bathe O., Carroll P.R., Chan J.M., Disaia P., Glenn P., Kelley R.K., Landen C.N., Phillips J., Prados M., Simko J., Smith-McCune K., VandenBerg S., Roggin K., Fehrenbach A., Kendler A., Sifri S., Steele R., Jimeno A., Carey F., Forgie I., Mannelli M., Carney M., Hernandez B., Campos B., Herold-Mende C., Jungk C., Unterberg A., von Deimling A., Bossler A., Galbraith J., Jacobus L., Knudson M., Knutson T., Ma D., Milhem M., Sigmund R., Godwin A.K., Madan R., Rosenthal H.G., Adebamowo C., Adebamowo S.N., Boussioutas A., Beer D., Giordano T., Mes-Masson A.-M., Saad F., Bocklage T., Landrum L., Mannel R., Moore K., Moxley K., Postier R., Walker J., Zuna R., Feldman M., Valdivieso F., Dhir R., Luketich J., Pinero E.M.M., Quintero-Aguilo M., Carlotti C.G., Dos Santos J.S., Kemp R., Sankarankuty A., Tirapelli D., Catto J., Agnew K., Swisher E., Creaney J., Robinson B., Shelley C.S., Godwin E.M., Kendall S., Shipman C., Bradford C., Carey T., Haddad A., Moyer J., Peterson L., Prince M., Rozek L., Wolf G., Bowman R., Fong K.M., Yang I., Korst R., Rathmell W.K., Fantacone-Campbell J.L., Hooke J.A., Kovatich A.J., Shriver C.D., DiPersio J., Drake B., Govindan R., Heath S., Ley T., Van Tine B., Westervelt P., Rubin M.A., Lee J.I., Aredes N.D., Mariamidze A., SAIC-F-Frederick, Inc, and Leidos Biomedical Research, Inc.
Subjects: Genetics and Molecular Biology (all), 0301 basic medicine, pan-cancer analysis, Cancer Genome Atlas Research Network, PD-L1 expression, medicine.disease_cause, Genome, Biochemistry, B7-H1 Antigen, Neoplasms, Databases, Genetic, LS2_1, LS4_6, CLASS DISCOVERY, 610 Medicine & health, 11 Medical and Health Sciences, GENE-EXPRESSION, Regulation of gene expression, Mutation, TRANSCRIPTIONAL ENHANCERS, Chromatin, GENOME, Gene Expression Regulation, Neoplastic, Survival Rate, enhancer expression, Enhancer Elements, Genetic, MAP, Immunotherapy, Life Sciences & Biomedicine, pan-cancer analysi, Biochemistry & Molecular Biology, aneuploidy, chromatin state, mutation burden, prognostic markers, The Cancer Genome Atlas, Biochemistry, Genetics and Molecular Biology (all), ORGANIZATION, Computational biology, Biology, General Biochemistry, Genetics and Molecular Biology, Article, NO, 03 medical and health sciences, medicine, Humans, Enhancer, Gene, Science & Technology, LANDSCAPE, IDENTIFICATION, Sequence Analysis, RNA, Biochemistry, Genetics and Molecular Biology(all), Cancer, Cell Biology, 06 Biological Sciences, medicine.disease, SUPER-ENHANCERS, 030104 developmental biology, PRINCIPLES, Expression quantitative trait loci, CROMATINA, prognostic marker, Developmental Biology, Genetics and Molecular Biology(all)
Abstract: The role of enhancers, a key class of non-coding regulatory DNA elements, in cancer development has increasingly been appreciated. Here, we present the detection and characterization of a large number of expressed enhancers in a genome-wide analysis of 8928 tumor samples across 33 cancer types using TCGA RNA-seq data. Compared with matched normal tissues, global enhancer activation was observed in most cancers. Across cancer types, global enhancer activity was positively associated with aneuploidy, but not mutation load, suggesting a hypothesis centered on “chromatin-state” to explain their interplay. Integrating eQTL, mRNA co-expression, and Hi-C data analysis, we developed a computational method to infer causal enhancer-gene interactions, revealing enhancers of clinically actionable genes. Having identified an enhancer ∼140 kb downstream of PD-L1, a major immunotherapy target, we validated it experimentally. This study provides a systematic view of enhancer activity in diverse tumor contexts and suggests the clinical implications of enhancers. Causal enhancer-target-gene relationships are inferred from a systematic analysis of 33 cancer types.
Published: 2018

20. Comprehensive Characterization of Cancer Driver Genes and Mutations

Author: Matthew H. Bailey, Collin Tokheim, Eduard Porta-Pardo, Sohini Sengupta, Denis Bertrand, Amila Weerasinghe, Antonio Colaprico, Michael C. Wendl, Jaegil Kim, Brendan Reardon, Patrick Kwok-Shing Ng, Kang Jin Jeong, Song Cao, Zixing Wang, Jianjiong Gao, Qingsong Gao, Fang Wang, Eric Minwei Liu, Loris Mularoni, Carlota Rubio-Perez, Niranjan Nagarajan, Isidro Cortés-Ciriano, Daniel Cui Zhou, Wen-Wei Liang, Julian M. Hess, Venkata D. Yellapantula, David Tamborero, Abel Gonzalez-Perez, Chayaporn Suphavilai, Jia Yu Ko, Ekta Khurana, Peter J. Park, Eliezer M. Van Allen, Han Liang, Michael S. Lawrence, Adam Godzik, Nuria Lopez-Bigas, Josh Stuart, David Wheeler, Gad Getz, Ken Chen, Alexander J. Lazar, Gordon B. Mills, Rachel Karchin, Li Ding, Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, David I. Heiman, Pei Lin, Sam Meier, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Yuexin Liu, Michael Miller, Sheila Reynolds, Ilya Shmulevich, Vesteinn Thorsson, Wei Zhang, Rehan Akbani, Bradley M. Broom, Apurva M. Hegde, Zhenlin Ju, Rupa S. Kanchi, Anil Korkut, Jun Li, Shiyun Ling, Wenbin Liu, Yiling Lu, Kwok-Shing Ng, Arvind Rao, Michael Ryan, Jing Wang, John N. Weinstein, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K. Chatila, Ino de Bruijn, Benjamin E. Gross, Zachary J. Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G. Nissan, Angelica Ochoa, Sarah M. Phillips, Ed Reznik, Francisco Sanchez-Vega, Chris Sander, Nikolaus Schultz, Robert Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, Joshua M. Stuart, Christopher K. Wong, Christina Yau, D. Neil Hayes, Joel S. Parker, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, A. Gordon Robertson, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Ashton C. Berger, Rameen Beroukhim, Andrew D. Cherniack, Carrie Cibulskis, Stacey B. Gabriel, Galen F. Gao, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju S. Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz S. Bootwalla, Phillip H. Lai, Dennis T. Maglinte, David J. Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Cheng Fan, Katherine A. Hoadley, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Amy H. Perou, Charles M. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Huihui Fan, Toshinori Hinoue, Peter W. Laird, Hui Shen, Wanding Zhou, Michelle Bellair, Kyle Chang, Kyle Covington, Chad J. Creighton, Huyen Dinh, HarshaVardhan Doddapaneni, Lawrence A. Donehower, Jennifer Drummond, Richard A. Gibbs, Robert Glenn, Walker Hale, Yi Han, Jianhong Hu, Viktoriya Korchina, Sandra Lee, Lora Lewis, Wei Li, Xiuping Liu, Margaret Morgan, Donna Morton, Donna Muzny, Jireh Santibanez, Margi Sheth, Eve Shinbrot, Linghua Wang, Min Wang, David A. Wheeler, Liu Xi, Fengmei Zhao, Julian Hess, Elizabeth L. Appelbaum, Matthew Bailey, Matthew G. Cordes, Catrina C. Fronick, Lucinda A. Fulton, Robert S. Fulton, Cyriac Kandoth, Elaine R. Mardis, Michael D. McLellan, Christopher A. Miller, Heather K. Schmidt, Richard K. Wilson, Daniel Crain, Erin Curley, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Mark Sherman, Eric Thompson, Peggy Yena, Jay Bowen, Julie M. Gastier-Foster, Mark Gerken, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Niall Corcoran, Tony Costello, Christopher Hovens, Andre L. Carvalho, Ana C. de Carvalho, José H. Fregnani, Adhemar Longatto-Filho, Rui M. Reis, Cristovam Scapulatempo-Neto, Henrique C.S. Silveira, Daniel O. Vidal, Andrew Burnette, Jennifer Eschbacher, Beth Hermes, Ardene Noss, Rosy Singh, Matthew L. Anderson, Patricia D. Castro, Michael Ittmann, David Huntsman, Bernard Kohl, Xuan Le, Richard Thorp, Chris Andry, Elizabeth R. Duffy, Vladimir Lyadov, Oxana Paklina, Galiya Setdikova, Alexey Shabunin, Mikhail Tavobilov, Christopher McPherson, Ronald Warnick, Ross Berkowitz, Daniel Cramer, Colleen Feltmate, Neil Horowitz, Adam Kibel, Michael Muto, Chandrajit P. Raut, Andrei Malykh, Jill S. Barnholtz-Sloan, Wendi Barrett, Karen Devine, Jordonna Fulop, Quinn T. Ostrom, Kristen Shimmel, Yingli Wolinsky, Andrew E. Sloan, Agostino De Rose, Felice Giuliante, Marc Goodman, Beth Y. Karlan, Curt H. Hagedorn, John Eckman, Jodi Harr, Jerome Myers, Kelinda Tucker, Leigh Anne Zach, Brenda Deyarmin, Hai Hu, Leonid Kvecher, Caroline Larson, Richard J. Mural, Stella Somiari, Ales Vicha, Tomas Zelinka, Joseph Bennett, Mary Iacocca, Brenda Rabeno, Patricia Swanson, Mathieu Latour, Louis Lacombe, Bernard Têtu, Alain Bergeron, Mary McGraw, Susan M. Staugaitis, John Chabot, Hanina Hibshoosh, Antonia Sepulveda, Tao Su, Timothy Wang, Olga Potapova, Olga Voronina, Laurence Desjardins, Odette Mariani, Sergio Roman-Roman, Xavier Sastre, Marc-Henri Stern, Feixiong Cheng, Sabina Signoretti, Andrew Berchuck, Darell Bigner, Eric Lipp, Jeffrey Marks, Shannon McCall, Roger McLendon, Angeles Secord, Alexis Sharp, Madhusmita Behera, Daniel J. Brat, Amy Chen, Keith Delman, Seth Force, Fadlo Khuri, Kelly Magliocca, Shishir Maithel, Jeffrey J. Olson, Taofeek Owonikoko, Alan Pickens, Suresh Ramalingam, Dong M. Shin, Gabriel Sica, Erwin G. Van Meir, Hongzheng Zhang, Wil Eijckenboom, Ad Gillis, Esther Korpershoek, Leendert Looijenga, Wolter Oosterhuis, Hans Stoop, Kim E. van Kessel, Ellen C. Zwarthoff, Chiara Calatozzolo, Lucia Cuppini, Stefania Cuzzubbo, Francesco DiMeco, Gaetano Finocchiaro, Luca Mattei, Alessandro Perin, Bianca Pollo, Chu Chen, John Houck, Pawadee Lohavanichbutr, Arndt Hartmann, Christine Stoehr, Robert Stoehr, Helge Taubert, Sven Wach, Bernd Wullich, Witold Kycler, Dawid Murawa, Maciej Wiznerowicz, Ki Chung, W. Jeffrey Edenfield, Julie Martin, Eric Baudin, Glenn Bubley, Raphael Bueno, Assunta De Rienzo, William G. Richards, Steven Kalkanis, Tom Mikkelsen, Houtan Noushmehr, Lisa Scarpace, Nicolas Girard, Marta Aymerich, Elias Campo, Eva Giné, Armando López Guillermo, Nguyen Van Bang, Phan Thi Hanh, Bui Duc Phu, Yufang Tang, Howard Colman, Kimberley Evason, Peter R. Dottino, John A. Martignetti, Hani Gabra, Hartmut Juhl, Teniola Akeredolu, Serghei Stepa, Dave Hoon, Keunsoo Ahn, Koo Jeong Kang, Felix Beuschlein, Anne Breggia, Michael Birrer, Debra Bell, Mitesh Borad, Alan H. Bryce, Erik Castle, Vishal Chandan, John Cheville, John A. Copland, Michael Farnell, Thomas Flotte, Nasra Giama, Thai Ho, Michael Kendrick, Jean-Pierre Kocher, Karla Kopp, Catherine Moser, David Nagorney, Daniel O’Brien, Brian Patrick O’Neill, Tushar Patel, Gloria Petersen, Florencia Que, Michael Rivera, Lewis Roberts, Robert Smallridge, Thomas Smyrk, Melissa Stanton, R. Houston Thompson, Michael Torbenson, Ju Dong Yang, Lizhi Zhang, Fadi Brimo, Jaffer A. Ajani, Ana Maria Angulo Gonzalez, Carmen Behrens, Jolanta Bondaruk, Russell Broaddus, Bogdan Czerniak, Bita Esmaeli, Junya Fujimoto, Jeffrey Gershenwald, Charles Guo, Christopher Logothetis, Funda Meric-Bernstam, Cesar Moran, Lois Ramondetta, David Rice, Anil Sood, Pheroze Tamboli, Timothy Thompson, Patricia Troncoso, Anne Tsao, Ignacio Wistuba, Candace Carter, Lauren Haydu, Peter Hersey, Valerie Jakrot, Hojabr Kakavand, Richard Kefford, Kenneth Lee, Georgina Long, Graham Mann, Michael Quinn, Robyn Saw, Richard Scolyer, Kerwin Shannon, Andrew Spillane, Jonathan Stretch, Maria Synott, John Thompson, James Wilmott, Hikmat Al-Ahmadie, Timothy A. Chan, Ronald Ghossein, Anuradha Gopalan, Douglas A. Levine, Victor Reuter, Samuel Singer, Bhuvanesh Singh, Nguyen Viet Tien, Thomas Broudy, Cyrus Mirsaidi, Praveen Nair, Paul Drwiega, Judy Miller, Jennifer Smith, Howard Zaren, Joong-Won Park, Nguyen Phi Hung, Electron Kebebew, W. Marston Linehan, Adam R. Metwalli, Karel Pacak, Peter A. Pinto, Mark Schiffman, Laura S. Schmidt, Cathy D. Vocke, Nicolas Wentzensen, Robert Worrell, Hannah Yang, Marc Moncrieff, Chandra Goparaju, Jonathan Melamed, Harvey Pass, Natalia Botnariuc, Irina Caraman, Mircea Cernat, Inga Chemencedji, Adrian Clipca, Serghei Doruc, Ghenadie Gorincioi, Sergiu Mura, Maria Pirtac, Irina Stancul, Diana Tcaciuc, Monique Albert, Iakovina Alexopoulou, Angel Arnaout, John Bartlett, Jay Engel, Sebastien Gilbert, Jeremy Parfitt, Harman Sekhon, George Thomas, Doris M. Rassl, Robert C. Rintoul, Carlo Bifulco, Raina Tamakawa, Walter Urba, Nicholas Hayward, Henri Timmers, Anna Antenucci, Francesco Facciolo, Gianluca Grazi, Mirella Marino, Roberta Merola, Ronald de Krijger, Anne-Paule Gimenez-Roqueplo, Alain Piché, Simone Chevalier, Ginette McKercher, Kivanc Birsoy, Gene Barnett, Cathy Brewer, Carol Farver, Theresa Naska, Nathan A. Pennell, Daniel Raymond, Cathy Schilero, Kathy Smolenski, Felicia Williams, Carl Morrison, Jeffrey A. Borgia, Michael J. Liptay, Mark Pool, Christopher W. Seder, Kerstin Junker, Larsson Omberg, Mikhail Dinkin, George Manikhas, Domenico Alvaro, Maria Consiglia Bragazzi, Vincenzo Cardinale, Guido Carpino, Eugenio Gaudio, David Chesla, Sandra Cottingham, Michael Dubina, Fedor Moiseenko, Renumathy Dhanasekaran, Karl-Friedrich Becker, Klaus-Peter Janssen, Julia Slotta-Huspenina, Mohamed H. Abdel-Rahman, Dina Aziz, Sue Bell, Colleen M. Cebulla, Amy Davis, Rebecca Duell, J. Bradley Elder, Joe Hilty, Bahavna Kumar, James Lang, Norman L. Lehman, Randy Mandt, Phuong Nguyen, Robert Pilarski, Karan Rai, Lynn Schoenfield, Kelly Senecal, Paul Wakely, Paul Hansen, Ronald Lechan, James Powers, Arthur Tischler, William E. Grizzle, Katherine C. Sexton, Alison Kastl, Joel Henderson, Sima Porten, Jens Waldmann, Martin Fassnacht, Sylvia L. Asa, Dirk Schadendorf, Marta Couce, Markus Graefen, Hartwig Huland, Guido Sauter, Thorsten Schlomm, Ronald Simon, Pierre Tennstedt, Oluwole Olabode, Mark Nelson, Oliver Bathe, Peter R. Carroll, June M. Chan, Philip Disaia, Pat Glenn, Robin K. Kelley, Charles N. Landen, Joanna Phillips, Michael Prados, Jeffry Simko, Karen Smith-McCune, Scott VandenBerg, Kevin Roggin, Ashley Fehrenbach, Ady Kendler, Suzanne Sifri, Ruth Steele, Antonio Jimeno, Francis Carey, Ian Forgie, Massimo Mannelli, Michael Carney, Brenda Hernandez, Benito Campos, Christel Herold-Mende, Christin Jungk, Andreas Unterberg, Andreas von Deimling, Aaron Bossler, Joseph Galbraith, Laura Jacobus, Michael Knudson, Tina Knutson, Deqin Ma, Mohammed Milhem, Rita Sigmund, Andrew K. Godwin, Rashna Madan, Howard G. Rosenthal, Clement Adebamowo, Sally N. Adebamowo, Alex Boussioutas, David Beer, Thomas Giordano, Anne-Marie Mes-Masson, Fred Saad, Therese Bocklage, Lisa Landrum, Robert Mannel, Kathleen Moore, Katherine Moxley, Russel Postier, Joan Walker, Rosemary Zuna, Michael Feldman, Federico Valdivieso, Rajiv Dhir, James Luketich, Edna M. Mora Pinero, Mario Quintero-Aguilo, Carlos Gilberto Carlotti, Jose Sebastião Dos Santos, Rafael Kemp, Ajith Sankarankuty, Daniela Tirapelli, James Catto, Kathy Agnew, Elizabeth Swisher, Jenette Creaney, Bruce Robinson, Carl Simon Shelley, Eryn M. Godwin, Sara Kendall, Cassaundra Shipman, Carol Bradford, Thomas Carey, Andrea Haddad, Jeffey Moyer, Lisa Peterson, Mark Prince, Laura Rozek, Gregory Wolf, Rayleen Bowman, Kwun M. Fong, Ian Yang, Robert Korst, W. Kimryn Rathmell, J. Leigh Fantacone-Campbell, Jeffrey A. Hooke, Albert J. Kovatich, Craig D. Shriver, John DiPersio, Bettina Drake, Ramaswamy Govindan, Sharon Heath, Timothy Ley, Brian Van Tine, Peter Westervelt, Mark A. Rubin, Jung Il Lee, Natália D. Aredes, Armaz Mariamidze, Bailey M.H., Tokheim C., Porta-Pardo E., Sengupta S., Bertrand D., Weerasinghe A., Colaprico A., Wendl M.C., Kim J., Reardon B., Ng P.K.-S., Jeong K.J., Cao S., Wang Z., Gao J., Gao Q., Wang F., Liu E.M., Mularoni L., Rubio-Perez C., Nagarajan N., Cortes-Ciriano I., Zhou D.C., Liang W.-W., Hess J.M., Yellapantula V.D., Tamborero D., Gonzalez-Perez A., Suphavilai C., Ko J.Y., Khurana E., Park P.J., Van Allen E.M., Liang H., Caesar-Johnson S.J., Demchok J.A., Felau I., Kasapi M., Ferguson M.L., Hutter C.M., Sofia H.J., Tarnuzzer R., Yang L., Zenklusen J.C., Zhang J.J., Chudamani S., Liu J., Lolla L., Naresh R., Pihl T., Sun Q., Wan Y., Wu Y., Cho J., DeFreitas T., Frazer S., Gehlenborg N., Getz G., Heiman D.I., Lawrence M.S., Lin P., Meier S., Noble M.S., Saksena G., Voet D., Zhang H., Bernard B., Chambwe N., Dhankani V., Knijnenburg T., Kramer R., Leinonen K., Liu Y., Miller M., Reynolds S., Shmulevich I., Thorsson V., Zhang W., Akbani R., Broom B.M., Hegde A.M., Ju Z., Kanchi R.S., Korkut A., Li J., Ling S., Liu W., Lu Y., Mills G.B., Ng K.-S., Rao A., Ryan M., Wang J., Weinstein J.N., Zhang J., Abeshouse A., Armenia J., Chakravarty D., Chatila W.K., de Bruijn I., Gross B.E., Heins Z.J., Kundra R., La K., Ladanyi M., Luna A., Nissan M.G., Ochoa A., Phillips S.M., Reznik E., Sanchez-Vega F., Sander C., Schultz N., Sheridan R., Sumer S.O., Sun Y., Taylor B.S., Anur P., Peto M., Spellman P., Benz C., Stuart J.M., Wong C.K., Yau C., Hayes D.N., Parker J.S., Wilkerson M.D., Ally A., Balasundaram M., Bowlby R., Brooks D., Carlsen R., Chuah E., Dhalla N., Holt R., Jones S.J.M., Kasaian K., Lee D., Ma Y., Marra M.A., Mayo M., Moore R.A., Mungall A.J., Mungall K., Robertson A.G., Sadeghi S., Schein J.E., Sipahimalani P., Tam A., Thiessen N., Tse K., Wong T., Berger A.C., Beroukhim R., Cherniack A.D., Cibulskis C., Gabriel S.B., Gao G.F., Ha G., Meyerson M., Schumacher S.E., Shih J., Kucherlapati M.H., Kucherlapati R.S., Baylin S., Cope L., Danilova L., Bootwalla M.S., Lai P.H., Maglinte D.T., Van Den Berg D.J., Weisenberger D.J., Auman J.T., Balu S., Bodenheimer T., Fan C., Hoadley K.A., Hoyle A.P., Jefferys S.R., Jones C.D., Meng S., Mieczkowski P.A., Mose L.E., Perou A.H., Perou C.M., Roach J., Shi Y., Simons J.V., Skelly T., Soloway M.G., Tan D., Veluvolu U., Fan H., Hinoue T., Laird P.W., Shen H., Zhou W., Bellair M., Chang K., Covington K., Creighton C.J., Dinh H., Doddapaneni H., Donehower L.A., Drummond J., Gibbs R.A., Glenn R., Hale W., Han Y., Hu J., Korchina V., Lee S., Lewis L., Li W., Liu X., Morgan M., Morton D., Muzny D., Santibanez J., Sheth M., Shinbrot E., Wang L., Wang M., Wheeler D.A., Xi L., Zhao F., Hess J., Appelbaum E.L., Bailey M., Cordes M.G., Ding L., Fronick C.C., Fulton L.A., Fulton R.S., Kandoth C., Mardis E.R., McLellan M.D., Miller C.A., Schmidt H.K., Wilson R.K., Crain D., Curley E., Gardner J., Lau K., Mallery D., Morris S., Paulauskis J., Penny R., Shelton C., Shelton T., Sherman M., Thompson E., Yena P., Bowen J., Gastier-Foster J.M., Gerken M., Leraas K.M., Lichtenberg T.M., Ramirez N.C., Wise L., Zmuda E., Corcoran N., Costello T., Hovens C., Carvalho A.L., de Carvalho A.C., Fregnani J.H., Longatto-Filho A., Reis R.M., Scapulatempo-Neto C., Silveira H.C.S., Vidal D.O., Burnette A., Eschbacher J., Hermes B., Noss A., Singh R., Anderson M.L., Castro P.D., Ittmann M., Huntsman D., Kohl B., Le X., Thorp R., Andry C., Duffy E.R., Lyadov V., Paklina O., Setdikova G., Shabunin A., Tavobilov M., McPherson C., Warnick R., Berkowitz R., Cramer D., Feltmate C., Horowitz N., Kibel A., Muto M., Raut C.P., Malykh A., Barnholtz-Sloan J.S., Barrett W., Devine K., Fulop J., Ostrom Q.T., Shimmel K., Wolinsky Y., Sloan A.E., De Rose A., Giuliante F., Goodman M., Karlan B.Y., Hagedorn C.H., Eckman J., Harr J., Myers J., Tucker K., Zach L.A., Deyarmin B., Hu H., Kvecher L., Larson C., Mural R.J., Somiari S., Vicha A., Zelinka T., Bennett J., Iacocca M., Rabeno B., Swanson P., Latour M., Lacombe L., Tetu B., Bergeron A., McGraw M., Staugaitis S.M., Chabot J., Hibshoosh H., Sepulveda A., Su T., Wang T., Potapova O., Voronina O., Desjardins L., Mariani O., Roman-Roman S., Sastre X., Stern M.-H., Cheng F., Signoretti S., Berchuck A., Bigner D., Lipp E., Marks J., McCall S., McLendon R., Secord A., Sharp A., Behera M., Brat D.J., Chen A., Delman K., Force S., Khuri F., Magliocca K., Maithel S., Olson J.J., Owonikoko T., Pickens A., Ramalingam S., Shin D.M., Sica G., Van Meir E.G., Eijckenboom W., Gillis A., Korpershoek E., Looijenga L., Oosterhuis W., Stoop H., van Kessel K.E., Zwarthoff E.C., Calatozzolo C., Cuppini L., Cuzzubbo S., DiMeco F., Finocchiaro G., Mattei L., Perin A., Pollo B., Chen C., Houck J., Lohavanichbutr P., Hartmann A., Stoehr C., Stoehr R., Taubert H., Wach S., Wullich B., Kycler W., Murawa D., Wiznerowicz M., Chung K., Edenfield W.J., Martin J., Baudin E., Bubley G., Bueno R., De Rienzo A., Richards W.G., Kalkanis S., Mikkelsen T., Noushmehr H., Scarpace L., Girard N., Aymerich M., Campo E., Gine E., Guillermo A.L., Van Bang N., Hanh P.T., Phu B.D., Tang Y., Colman H., Evason K., Dottino P.R., Martignetti J.A., Gabra H., Juhl H., Akeredolu T., Stepa S., Hoon D., Ahn K., Kang K.J., Beuschlein F., Breggia A., Birrer M., Bell D., Borad M., Bryce A.H., Castle E., Chandan V., Cheville J., Copland J.A., Farnell M., Flotte T., Giama N., Ho T., Kendrick M., Kocher J.-P., Kopp K., Moser C., Nagorney D., O'Brien D., O'Neill B.P., Patel T., Petersen G., Que F., Rivera M., Roberts L., Smallridge R., Smyrk T., Stanton M., Thompson R.H., Torbenson M., Yang J.D., Zhang L., Brimo F., Ajani J.A., Gonzalez A.M.A., Behrens C., Bondaruk J., Broaddus R., Czerniak B., Esmaeli B., Fujimoto J., Gershenwald J., Guo C., Lazar A.J., Logothetis C., Meric-Bernstam F., Moran C., Ramondetta L., Rice D., Sood A., Tamboli P., Thompson T., Troncoso P., Tsao A., Wistuba I., Carter C., Haydu L., Hersey P., Jakrot V., Kakavand H., Kefford R., Lee K., Long G., Mann G., Quinn M., Saw R., Scolyer R., Shannon K., Spillane A., Stretch J., Synott M., Thompson J., Wilmott J., Al-Ahmadie H., Chan T.A., Ghossein R., Gopalan A., Levine D.A., Reuter V., Singer S., Singh B., Tien N.V., Broudy T., Mirsaidi C., Nair P., Drwiega P., Miller J., Smith J., Zaren H., Park J.-W., Hung N.P., Kebebew E., Linehan W.M., Metwalli A.R., Pacak K., Pinto P.A., Schiffman M., Schmidt L.S., Vocke C.D., Wentzensen N., Worrell R., Yang H., Moncrieff M., Goparaju C., Melamed J., Pass H., Botnariuc N., Caraman I., Cernat M., Chemencedji I., Clipca A., Doruc S., Gorincioi G., Mura S., Pirtac M., Stancul I., Tcaciuc D., Albert M., Alexopoulou I., Arnaout A., Bartlett J., Engel J., Gilbert S., Parfitt J., Sekhon H., Thomas G., Rassl D.M., Rintoul R.C., Bifulco C., Tamakawa R., Urba W., Hayward N., Timmers H., Antenucci A., Facciolo F., Grazi G., Marino M., Merola R., de Krijger R., Gimenez-Roqueplo A.-P., Piche A., Chevalier S., McKercher G., Birsoy K., Barnett G., Brewer C., Farver C., Naska T., Pennell N.A., Raymond D., Schilero C., Smolenski K., Williams F., Morrison C., Borgia J.A., Liptay M.J., Pool M., Seder C.W., Junker K., Omberg L., Dinkin M., Manikhas G., Alvaro D., Bragazzi M.C., Cardinale V., Carpino G., Gaudio E., Chesla D., Cottingham S., Dubina M., Moiseenko F., Dhanasekaran R., Becker K.-F., Janssen K.-P., Slotta-Huspenina J., Abdel-Rahman M.H., Aziz D., Bell S., Cebulla C.M., Davis A., Duell R., Elder J.B., Hilty J., Kumar B., Lang J., Lehman N.L., Mandt R., Nguyen P., Pilarski R., Rai K., Schoenfield L., Senecal K., Wakely P., Hansen P., Lechan R., Powers J., Tischler A., Grizzle W.E., Sexton K.C., Kastl A., Henderson J., Porten S., Waldmann J., Fassnacht M., Asa S.L., Schadendorf D., Couce M., Graefen M., Huland H., Sauter G., Schlomm T., Simon R., Tennstedt P., Olabode O., Nelson M., Bathe O., Carroll P.R., Chan J.M., Disaia P., Glenn P., Kelley R.K., Landen C.N., Phillips J., Prados M., Simko J., Smith-McCune K., VandenBerg S., Roggin K., Fehrenbach A., Kendler A., Sifri S., Steele R., Jimeno A., Carey F., Forgie I., Mannelli M., Carney M., Hernandez B., Campos B., Herold-Mende C., Jungk C., Unterberg A., von Deimling A., Bossler A., Galbraith J., Jacobus L., Knudson M., Knutson T., Ma D., Milhem M., Sigmund R., Godwin A.K., Madan R., Rosenthal H.G., Adebamowo C., Adebamowo S.N., Boussioutas A., Beer D., Giordano T., Mes-Masson A.-M., Saad F., Bocklage T., Landrum L., Mannel R., Moore K., Moxley K., Postier R., Walker J., Zuna R., Feldman M., Valdivieso F., Dhir R., Luketich J., Pinero E.M.M., Quintero-Aguilo M., Carlotti C.G., Dos Santos J.S., Kemp R., Sankarankuty A., Tirapelli D., Catto J., Agnew K., Swisher E., Creaney J., Robinson B., Shelley C.S., Godwin E.M., Kendall S., Shipman C., Bradford C., Carey T., Haddad A., Moyer J., Peterson L., Prince M., Rozek L., Wolf G., Bowman R., Fong K.M., Yang I., Korst R., Rathmell W.K., Fantacone-Campbell J.L., Hooke J.A., Kovatich A.J., Shriver C.D., DiPersio J., Drake B., Govindan R., Heath S., Ley T., Van Tine B., Westervelt P., Rubin M.A., Lee J.I., Aredes N.D., Mariamidze A., Godzik A., Lopez-Bigas N., Stuart J., Wheeler D., Chen K., and Karchin R.
Subjects: 0301 basic medicine, Oncology, Entropy, Programmed Cell Death 1 Receptor, biochemistry, genetics, molecular Biology (all), Biochemistry, B7-H1 Antigen, structure analysi, Principal Component Analysi, Neoplasms, Databases, Genetic, LS2_1, LS4_6, Missense mutation, Statistical analysis, 610 Medicine & health, Exome sequencing, Confusion, Principal Component Analysis, Melanoma, Sciences bio-médicales et agricoles, structure analysis, Algorithm, oncology, Cancer gene, Adenocarcinoma, Microsatellite Instability, ALGORITMOS, medicine.symptom, Algorithms, Human, medicine.medical_specialty, driver gene discovery, Computational biology, Biology, Characterization (mathematics), General Biochemistry, Genetics and Molecular Biology, Article, NO, 03 medical and health sciences, Internal medicine, medicine, Humans, mutations of clinical relevance, Gene, Biochemistry, Genetics and Molecular Biology(all), Microsatellite instability, Computational Biology, Cancer, medicine.disease, Cancérologie, 030104 developmental biology, Precision oncology, Mutation, Neoplasm, Human genome, Colon adenocarcinoma, human activities, Genetics and Molecular Biology(all)
Abstract: Identifying molecular cancer drivers is critical for precision oncology. Multiple advanced algorithms to identify drivers now exist, but systematic attempts to combine and optimize them on large datasets are few. We report a PanCancer and PanSoftware analysis spanning 9,423 tumor exomes (comprising all 33 of The Cancer Genome Atlas projects) and using 26 computational tools to catalog driver genes and mutations. We identify 299 driver genes with implications regarding their anatomical sites and cancer/cell types. Sequence- and structure-based analyses identified >3,400 putative missense driver mutations supported by multiple lines of evidence. Experimental validation confirmed 60%–85% of predicted mutations as likely drivers. We found that >300 MSI tumors are associated with high PD-1/PD-L1, and 57% of tumors analyzed harbor putative clinically actionable events. Our study represents the most comprehensive discovery of cancer genes and mutations to date and will serve as a blueprint for future biological and clinical endeavors. A comprehensive analysis of oncogenic driver genes and mutations in >9,000 tumors across 33 cancer types highlights the prevalence of clinically actionable cancer driver events in TCGA tumor samples., 0, info:eu-repo/semantics/published
Published: 2018

21. Genomic and functional approaches to understanding cancer aneuploidy

Author: Alison M. Taylor, Juliann Shih, Gavin Ha, Galen F. Gao, Xiaoyang Zhang, Ashton C. Berger, Steven E. Schumacher, Chen Wang, Hai Hu, Jianfang Liu, Alexander J. Lazar, Andrew D. Cherniack, Rameen Beroukhim, Matthew Meyerson, Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, Gad Getz, David I. Heiman, Jaegil Kim, Michael S. Lawrence, Pei Lin, Sam Meier, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Yuexin Liu, Michael Miller, Sheila Reynolds, Ilya Shmulevich, Vesteinn Thorsson, Wei Zhang, Rehan Akbani, Bradley M. Broom, Apurva M. Hegde, Zhenlin Ju, Rupa S. Kanchi, Anil Korkut, Jun Li, Han Liang, Shiyun Ling, Wenbin Liu, Yiling Lu, Gordon B. Mills, Kwok-Shing Ng, Arvind Rao, Michael Ryan, Jing Wang, John N. Weinstein, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K. Chatila, Ino de Bruijn, Jianjiong Gao, Benjamin E. Gross, Zachary J. Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G. Nissan, Angelica Ochoa, Sarah M. Phillips, Ed Reznik, Francisco Sanchez-Vega, Chris Sander, Nikolaus Schultz, Robert Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, Joshua M. Stuart, Christopher K. Wong, Christina Yau, D. Neil Hayes, Joel S. Parker, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, A. Gordon Robertson, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Carrie Cibulskis, Stacey B. Gabriel, Melanie H. Kucherlapati, Raju S. Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz S. Bootwalla, Phillip H. Lai, Dennis T. Maglinte, David J. Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Cheng Fan, Katherine A. Hoadley, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Amy H. Perou, Charles M. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Huihui Fan, Toshinori Hinoue, Peter W. Laird, Hui Shen, Wanding Zhou, Michelle Bellair, Kyle Chang, Kyle Covington, Chad J. Creighton, Huyen Dinh, HarshaVardhan Doddapaneni, Lawrence A. Donehower, Jennifer Drummond, Richard A. Gibbs, Robert Glenn, Walker Hale, Yi Han, Jianhong Hu, Viktoriya Korchina, Sandra Lee, Lora Lewis, Wei Li, Xiuping Liu, Margaret Morgan, Donna Morton, Donna Muzny, Jireh Santibanez, Margi Sheth, Eve Shinbrot, Linghua Wang, Min Wang, David A. Wheeler, Liu Xi, Fengmei Zhao, Julian Hess, Elizabeth L. Appelbaum, Matthew Bailey, Matthew G. Cordes, Li Ding, Catrina C. Fronick, Lucinda A. Fulton, Robert S. Fulton, Cyriac Kandoth, Elaine R. Mardis, Michael D. McLellan, Christopher A. Miller, Heather K. Schmidt, Richard K. Wilson, Daniel Crain, Erin Curley, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Mark Sherman, Eric Thompson, Peggy Yena, Jay Bowen, Julie M. Gastier-Foster, Mark Gerken, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Niall Corcoran, Tony Costello, Christopher Hovens, Andre L. Carvalho, Ana C. de Carvalho, José H. Fregnani, Adhemar Longatto-Filho, Rui M. Reis, Cristovam Scapulatempo-Neto, Henrique C.S. Silveira, Daniel O. Vidal, Andrew Burnette, Jennifer Eschbacher, Beth Hermes, Ardene Noss, Rosy Singh, Matthew L. Anderson, Patricia D. Castro, Michael Ittmann, David Huntsman, Bernard Kohl, Xuan Le, Richard Thorp, Chris Andry, Elizabeth R. Duffy, Vladimir Lyadov, Oxana Paklina, Galiya Setdikova, Alexey Shabunin, Mikhail Tavobilov, Christopher McPherson, Ronald Warnick, Ross Berkowitz, Daniel Cramer, Colleen Feltmate, Neil Horowitz, Adam Kibel, Michael Muto, Chandrajit P. Raut, Andrei Malykh, Jill S. Barnholtz-Sloan, Wendi Barrett, Karen Devine, Jordonna Fulop, Quinn T. Ostrom, Kristen Shimmel, Yingli Wolinsky, Andrew E. Sloan, Agostino De Rose, Felice Giuliante, Marc Goodman, Beth Y. Karlan, Curt H. Hagedorn, John Eckman, Jodi Harr, Jerome Myers, Kelinda Tucker, Leigh Anne Zach, Brenda Deyarmin, Leonid Kvecher, Caroline Larson, Richard J. Mural, Stella Somiari, Ales Vicha, Tomas Zelinka, Joseph Bennett, Mary Iacocca, Brenda Rabeno, Patricia Swanson, Mathieu Latour, Louis Lacombe, Bernard Têtu, Alain Bergeron, Mary McGraw, Susan M. Staugaitis, John Chabot, Hanina Hibshoosh, Antonia Sepulveda, Tao Su, Timothy Wang, Olga Potapova, Olga Voronina, Laurence Desjardins, Odette Mariani, Sergio Roman-Roman, Xavier Sastre, Marc-Henri Stern, Feixiong Cheng, Sabina Signoretti, Andrew Berchuck, Darell Bigner, Eric Lipp, Jeffrey Marks, Shannon McCall, Roger McLendon, Angeles Secord, Alexis Sharp, Madhusmita Behera, Daniel J. Brat, Amy Chen, Keith Delman, Seth Force, Fadlo Khuri, Kelly Magliocca, Shishir Maithel, Jeffrey J. Olson, Taofeek Owonikoko, Alan Pickens, Suresh Ramalingam, Dong M. Shin, Gabriel Sica, Erwin G. Van Meir, Hongzheng Zhang, Wil Eijckenboom, Ad Gillis, Esther Korpershoek, Leendert Looijenga, Wolter Oosterhuis, Hans Stoop, Kim E. van Kessel, Ellen C. Zwarthoff, Chiara Calatozzolo, Lucia Cuppini, Stefania Cuzzubbo, Francesco DiMeco, Gaetano Finocchiaro, Luca Mattei, Alessandro Perin, Bianca Pollo, Chu Chen, John Houck, Pawadee Lohavanichbutr, Arndt Hartmann, Christine Stoehr, Robert Stoehr, Helge Taubert, Sven Wach, Bernd Wullich, Witold Kycler, Dawid Murawa, Maciej Wiznerowicz, Ki Chung, W. Jeffrey Edenfield, Julie Martin, Eric Baudin, Glenn Bubley, Raphael Bueno, Assunta De Rienzo, William G. Richards, Steven Kalkanis, Tom Mikkelsen, Houtan Noushmehr, Lisa Scarpace, Nicolas Girard, Marta Aymerich, Elias Campo, Eva Giné, Armando López Guillermo, Nguyen Van Bang, Phan Thi Hanh, Bui Duc Phu, Yufang Tang, Howard Colman, Kimberley Evason, Peter R. Dottino, John A. Martignetti, Hani Gabra, Hartmut Juhl, Teniola Akeredolu, Serghei Stepa, Dave Hoon, Keunsoo Ahn, Koo Jeong Kang, Felix Beuschlein, Anne Breggia, Michael Birrer, Debra Bell, Mitesh Borad, Alan H. Bryce, Erik Castle, Vishal Chandan, John Cheville, John A. Copland, Michael Farnell, Thomas Flotte, Nasra Giama, Thai Ho, Michael Kendrick, Jean-Pierre Kocher, Karla Kopp, Catherine Moser, David Nagorney, Daniel O’Brien, Brian Patrick O’Neill, Tushar Patel, Gloria Petersen, Florencia Que, Michael Rivera, Lewis Roberts, Robert Smallridge, Thomas Smyrk, Melissa Stanton, R. Houston Thompson, Michael Torbenson, Ju Dong Yang, Lizhi Zhang, Fadi Brimo, Jaffer A. Ajani, Ana Maria Angulo Gonzalez, Carmen Behrens, Jolanta Bondaruk, Russell Broaddus, Bogdan Czerniak, Bita Esmaeli, Junya Fujimoto, Jeffrey Gershenwald, Charles Guo, Christopher Logothetis, Funda Meric-Bernstam, Cesar Moran, Lois Ramondetta, David Rice, Anil Sood, Pheroze Tamboli, Timothy Thompson, Patricia Troncoso, Anne Tsao, Ignacio Wistuba, Candace Carter, Lauren Haydu, Peter Hersey, Valerie Jakrot, Hojabr Kakavand, Richard Kefford, Kenneth Lee, Georgina Long, Graham Mann, Michael Quinn, Robyn Saw, Richard Scolyer, Kerwin Shannon, Andrew Spillane, Jonathan Stretch, Maria Synott, John Thompson, James Wilmott, Hikmat Al-Ahmadie, Timothy A. Chan, Ronald Ghossein, Anuradha Gopalan, Douglas A. Levine, Victor Reuter, Samuel Singer, Bhuvanesh Singh, Nguyen Viet Tien, Thomas Broudy, Cyrus Mirsaidi, Praveen Nair, Paul Drwiega, Judy Miller, Jennifer Smith, Howard Zaren, Joong-Won Park, Nguyen Phi Hung, Electron Kebebew, W. Marston Linehan, Adam R. Metwalli, Karel Pacak, Peter A. Pinto, Mark Schiffman, Laura S. Schmidt, Cathy D. Vocke, Nicolas Wentzensen, Robert Worrell, Hannah Yang, Marc Moncrieff, Chandra Goparaju, Jonathan Melamed, Harvey Pass, Natalia Botnariuc, Irina Caraman, Mircea Cernat, Inga Chemencedji, Adrian Clipca, Serghei Doruc, Ghenadie Gorincioi, Sergiu Mura, Maria Pirtac, Irina Stancul, Diana Tcaciuc, Monique Albert, Iakovina Alexopoulou, Angel Arnaout, John Bartlett, Jay Engel, Sebastien Gilbert, Jeremy Parfitt, Harman Sekhon, George Thomas, Doris M. Rassl, Robert C. Rintoul, Carlo Bifulco, Raina Tamakawa, Walter Urba, Nicholas Hayward, Henri Timmers, Anna Antenucci, Francesco Facciolo, Gianluca Grazi, Mirella Marino, Roberta Merola, Ronald de Krijger, Anne-Paule Gimenez-Roqueplo, Alain Piché, Simone Chevalier, Ginette McKercher, Kivanc Birsoy, Gene Barnett, Cathy Brewer, Carol Farver, Theresa Naska, Nathan A. Pennell, Daniel Raymond, Cathy Schilero, Kathy Smolenski, Felicia Williams, Carl Morrison, Jeffrey A. Borgia, Michael J. Liptay, Mark Pool, Christopher W. Seder, Kerstin Junker, Larsson Omberg, Mikhail Dinkin, George Manikhas, Domenico Alvaro, Maria Consiglia Bragazzi, Vincenzo Cardinale, Guido Carpino, Eugenio Gaudio, David Chesla, Sandra Cottingham, Michael Dubina, Fedor Moiseenko, Renumathy Dhanasekaran, Karl-Friedrich Becker, Klaus-Peter Janssen, Julia Slotta-Huspenina, Mohamed H. Abdel-Rahman, Dina Aziz, Sue Bell, Colleen M. Cebulla, Amy Davis, Rebecca Duell, J. Bradley Elder, Joe Hilty, Bahavna Kumar, James Lang, Norman L. Lehman, Randy Mandt, Phuong Nguyen, Robert Pilarski, Karan Rai, Lynn Schoenfield, Kelly Senecal, Paul Wakely, Paul Hansen, Ronald Lechan, James Powers, Arthur Tischler, William E. Grizzle, Katherine C. Sexton, Alison Kastl, Joel Henderson, Sima Porten, Jens Waldmann, Martin Fassnacht, Sylvia L. Asa, Dirk Schadendorf, Marta Couce, Markus Graefen, Hartwig Huland, Guido Sauter, Thorsten Schlomm, Ronald Simon, Pierre Tennstedt, Oluwole Olabode, Mark Nelson, Oliver Bathe, Peter R. Carroll, June M. Chan, Philip Disaia, Pat Glenn, Robin K. Kelley, Charles N. Landen, Joanna Phillips, Michael Prados, Jeffry Simko, Karen Smith-McCune, Scott VandenBerg, Kevin Roggin, Ashley Fehrenbach, Ady Kendler, Suzanne Sifri, Ruth Steele, Antonio Jimeno, Francis Carey, Ian Forgie, Massimo Mannelli, Michael Carney, Brenda Hernandez, Benito Campos, Christel Herold-Mende, Christin Jungk, Andreas Unterberg, Andreas von Deimling, Aaron Bossler, Joseph Galbraith, Laura Jacobus, Michael Knudson, Tina Knutson, Deqin Ma, Mohammed Milhem, Rita Sigmund, Andrew K. Godwin, Rashna Madan, Howard G. Rosenthal, Clement Adebamowo, Sally N. Adebamowo, Alex Boussioutas, David Beer, Thomas Giordano, Anne-Marie Mes-Masson, Fred Saad, Therese Bocklage, Lisa Landrum, Robert Mannel, Kathleen Moore, Katherine Moxley, Russel Postier, Joan Walker, Rosemary Zuna, Michael Feldman, Federico Valdivieso, Rajiv Dhir, James Luketich, Edna M. Mora Pinero, Mario Quintero-Aguilo, Carlos Gilberto Carlotti, Jose Sebastião Dos Santos, Rafael Kemp, Ajith Sankarankuty, Daniela Tirapelli, James Catto, Kathy Agnew, Elizabeth Swisher, Jenette Creaney, Bruce Robinson, Carl Simon Shelley, Eryn M. Godwin, Sara Kendall, Cassaundra Shipman, Carol Bradford, Thomas Carey, Andrea Haddad, Jeffey Moyer, Lisa Peterson, Mark Prince, Laura Rozek, Gregory Wolf, Rayleen Bowman, Kwun M. Fong, Ian Yang, Robert Korst, W. Kimryn Rathmell, J. Leigh Fantacone-Campbell, Jeffrey A. Hooke, Albert J. Kovatich, Craig D. Shriver, John DiPersio, Bettina Drake, Ramaswamy Govindan, Sharon Heath, Timothy Ley, Brian Van Tine, Peter Westervelt, Mark A. Rubin, Jung Il Lee, Natália D. Aredes, Armaz Mariamidze, SAIC-F-Frederick, Inc, Leidos Biomedical Research, Inc., Taylor A.M., Shih J., Ha G., Gao G.F., Zhang X., Berger A.C., Schumacher S.E., Wang C., Hu H., Liu J., Lazar A.J., Caesar-Johnson S.J., Demchok J.A., Felau I., Kasapi M., Ferguson M.L., Hutter C.M., Sofia H.J., Tarnuzzer R., Wang Z., Yang L., Zenklusen J.C., Zhang J.J., Chudamani S., Lolla L., Naresh R., Pihl T., Sun Q., Wan Y., Wu Y., Cho J., DeFreitas T., Frazer S., Gehlenborg N., Getz G., Heiman D.I., Kim J., Lawrence M.S., Lin P., Meier S., Noble M.S., Saksena G., Voet D., Zhang H., Bernard B., Chambwe N., Dhankani V., Knijnenburg T., Kramer R., Leinonen K., Liu Y., Miller M., Reynolds S., Shmulevich I., Thorsson V., Zhang W., Akbani R., Broom B.M., Hegde A.M., Ju Z., Kanchi R.S., Korkut A., Li J., Liang H., Ling S., Liu W., Lu Y., Mills G.B., Ng K.-S., Rao A., Ryan M., Wang J., Weinstein J.N., Zhang J., Abeshouse A., Armenia J., Chakravarty D., Chatila W.K., de Bruijn I., Gao J., Gross B.E., Heins Z.J., Kundra R., La K., Ladanyi M., Luna A., Nissan M.G., Ochoa A., Phillips S.M., Reznik E., Sanchez-Vega F., Sander C., Schultz N., Sheridan R., Sumer S.O., Sun Y., Taylor B.S., Anur P., Peto M., Spellman P., Benz C., Stuart J.M., Wong C.K., Yau C., Hayes D.N., Parker J.S., Wilkerson M.D., Ally A., Balasundaram M., Bowlby R., Brooks D., Carlsen R., Chuah E., Dhalla N., Holt R., Jones S.J.M., Kasaian K., Lee D., Ma Y., Marra M.A., Mayo M., Moore R.A., Mungall A.J., Mungall K., Robertson A.G., Sadeghi S., Schein J.E., Sipahimalani P., Tam A., Thiessen N., Tse K., Wong T., Beroukhim R., Cherniack A.D., Cibulskis C., Gabriel S.B., Meyerson M., Kucherlapati M.H., Kucherlapati R.S., Baylin S., Cope L., Danilova L., Bootwalla M.S., Lai P.H., Maglinte D.T., Van Den Berg D.J., Weisenberger D.J., Auman J.T., Balu S., Bodenheimer T., Fan C., Hoadley K.A., Hoyle A.P., Jefferys S.R., Jones C.D., Meng S., Mieczkowski P.A., Mose L.E., Perou A.H., Perou C.M., Roach J., Shi Y., Simons J.V., Skelly T., Soloway M.G., Tan D., Veluvolu U., Fan H., Hinoue T., Laird P.W., Shen H., Zhou W., Bellair M., Chang K., Covington K., Creighton C.J., Dinh H., Doddapaneni H., Donehower L.A., Drummond J., Gibbs R.A., Glenn R., Hale W., Han Y., Hu J., Korchina V., Lee S., Lewis L., Li W., Liu X., Morgan M., Morton D., Muzny D., Santibanez J., Sheth M., Shinbrot E., Wang L., Wang M., Wheeler D.A., Xi L., Zhao F., Hess J., Appelbaum E.L., Bailey M., Cordes M.G., Ding L., Fronick C.C., Fulton L.A., Fulton R.S., Kandoth C., Mardis E.R., McLellan M.D., Miller C.A., Schmidt H.K., Wilson R.K., Crain D., Curley E., Gardner J., Lau K., Mallery D., Morris S., Paulauskis J., Penny R., Shelton C., Shelton T., Sherman M., Thompson E., Yena P., Bowen J., Gastier-Foster J.M., Gerken M., Leraas K.M., Lichtenberg T.M., Ramirez N.C., Wise L., Zmuda E., Corcoran N., Costello T., Hovens C., Carvalho A.L., de Carvalho A.C., Fregnani J.H., Longatto-Filho A., Reis R.M., Scapulatempo-Neto C., Silveira H.C.S., Vidal D.O., Burnette A., Eschbacher J., Hermes B., Noss A., Singh R., Anderson M.L., Castro P.D., Ittmann M., Huntsman D., Kohl B., Le X., Thorp R., Andry C., Duffy E.R., Lyadov V., Paklina O., Setdikova G., Shabunin A., Tavobilov M., McPherson C., Warnick R., Berkowitz R., Cramer D., Feltmate C., Horowitz N., Kibel A., Muto M., Raut C.P., Malykh A., Barnholtz-Sloan J.S., Barrett W., Devine K., Fulop J., Ostrom Q.T., Shimmel K., Wolinsky Y., Sloan A.E., De Rose A., Giuliante F., Goodman M., Karlan B.Y., Hagedorn C.H., Eckman J., Harr J., Myers J., Tucker K., Zach L.A., Deyarmin B., Kvecher L., Larson C., Mural R.J., Somiari S., Vicha A., Zelinka T., Bennett J., Iacocca M., Rabeno B., Swanson P., Latour M., Lacombe L., Tetu B., Bergeron A., McGraw M., Staugaitis S.M., Chabot J., Hibshoosh H., Sepulveda A., Su T., Wang T., Potapova O., Voronina O., Desjardins L., Mariani O., Roman-Roman S., Sastre X., Stern M.-H., Cheng F., Signoretti S., Berchuck A., Bigner D., Lipp E., Marks J., McCall S., McLendon R., Secord A., Sharp A., Behera M., Brat D.J., Chen A., Delman K., Force S., Khuri F., Magliocca K., Maithel S., Olson J.J., Owonikoko T., Pickens A., Ramalingam S., Shin D.M., Sica G., Van Meir E.G., Eijckenboom W., Gillis A., Korpershoek E., Looijenga L., Oosterhuis W., Stoop H., van Kessel K.E., Zwarthoff E.C., Calatozzolo C., Cuppini L., Cuzzubbo S., DiMeco F., Finocchiaro G., Mattei L., Perin A., Pollo B., Chen C., Houck J., Lohavanichbutr P., Hartmann A., Stoehr C., Stoehr R., Taubert H., Wach S., Wullich B., Kycler W., Murawa D., Wiznerowicz M., Chung K., Edenfield W.J., Martin J., Baudin E., Bubley G., Bueno R., De Rienzo A., Richards W.G., Kalkanis S., Mikkelsen T., Noushmehr H., Scarpace L., Girard N., Aymerich M., Campo E., Gine E., Guillermo A.L., Van Bang N., Hanh P.T., Phu B.D., Tang Y., Colman H., Evason K., Dottino P.R., Martignetti J.A., Gabra H., Juhl H., Akeredolu T., Stepa S., Hoon D., Ahn K., Kang K.J., Beuschlein F., Breggia A., Birrer M., Bell D., Borad 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Moiseenko F., Dhanasekaran R., Becker K.-F., Janssen K.-P., Slotta-Huspenina J., Abdel-Rahman M.H., Aziz D., Bell S., Cebulla C.M., Davis A., Duell R., Elder J.B., Hilty J., Kumar B., Lang J., Lehman N.L., Mandt R., Nguyen P., Pilarski R., Rai K., Schoenfield L., Senecal K., Wakely P., Hansen P., Lechan R., Powers J., Tischler A., Grizzle W.E., Sexton K.C., Kastl A., Henderson J., Porten S., Waldmann J., Fassnacht M., Asa S.L., Schadendorf D., Couce M., Graefen M., Huland H., Sauter G., Schlomm T., Simon R., Tennstedt P., Olabode O., Nelson M., Bathe O., Carroll P.R., Chan J.M., Disaia P., Glenn P., Kelley R.K., Landen C.N., Phillips J., Prados M., Simko J., Smith-McCune K., VandenBerg S., Roggin K., Fehrenbach A., Kendler A., Sifri S., Steele R., Jimeno A., Carey F., Forgie I., Mannelli M., Carney M., Hernandez B., Campos B., Herold-Mende C., Jungk C., Unterberg A., von Deimling A., Bossler A., Galbraith J., Jacobus L., Knudson M., Knutson T., Ma D., Milhem M., Sigmund R., Godwin A.K., Madan R., Rosenthal H.G., Adebamowo C., Adebamowo S.N., Boussioutas A., Beer D., Giordano T., Mes-Masson A.-M., Saad F., Bocklage T., Landrum L., Mannel R., Moore K., Moxley K., Postier R., Walker J., Zuna R., Feldman M., Valdivieso F., Dhir R., Luketich J., Mora Pinero E.M., Quintero-Aguilo M., Carlotti C.G., Dos Santos J.S., Kemp R., Sankarankuty A., Tirapelli D., Catto J., Agnew K., Swisher E., Creaney J., Robinson B., Shelley C.S., Godwin E.M., Kendall S., Shipman C., Bradford C., Carey T., Haddad A., Moyer J., Peterson L., Prince M., Rozek L., Wolf G., Bowman R., Fong K.M., Yang I., Korst R., Rathmell W.K., Fantacone-Campbell J.L., Hooke J.A., Kovatich A.J., Shriver C.D., DiPersio J., Drake B., Govindan R., Heath S., Ley T., Van Tine B., Westervelt P., Rubin M.A., Lee J.I., Aredes N.D., and Mariamidze A.
Subjects: 0301 basic medicine, Cancer Research, Aneuploidy, Cancer Genome Atlas Research Network, CHROMOSOMAL INSTABILITY, Genome, EXPRESSION PROFILES, Mutation Rate, Chromosome instability, Gene duplication, MULTIPLE, Databases, Genetic, LS2_1, lung squamous cell carcinoma, LS4_6, 610 Medicine & health, Genetics, Cell Cycle, PROLIFERATION, cancer genomic, Genomics, PROLIFERAÇÃO CELULAR, SQUAMOUS-CELL CARCINOMAS, Oncology, Chromosome Arm, Carcinoma, Squamous Cell, Chromosomes, Human, Pair 3, Chromosome Deletion, aneuploidy, cancer genomics, genome engineering, Life Sciences & Biomedicine, Human, COPY-NUMBER ALTERATION, Biology, Chromosome Aberration, Article, NO, 03 medical and health sciences, Germline mutation, LUNG-CANCER, REVEALS, medicine, Humans, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Cell Proliferation, Chromosome Aberrations, Science & Technology, LANDSCAPE, Chromosome, Cell Biology, medicine.disease, DELETIONS, 030104 developmental biology, Chromosome 3, Genomic, Tumor Suppressor Protein p53, 1109 Neurosciences
Abstract: Aneuploidy, whole chromosome or chromosome arm imbalance, is a near-universal characteristic of human cancers. In 10,522 cancer genomes from The Cancer Genome Atlas, aneuploidy was correlated with TP53 mutation, somatic mutation rate, and expression of proliferation genes. Aneuploidy was anti-correlated with expression of immune signaling genes, due to decreased leukocyte infiltrates in high-aneuploidy samples. Chromosome arm-level alterations show cancer-specific patterns, including loss of chromosome arm 3p in squamous cancers. We applied genome engineering to delete 3p in lung cells, causing decreased proliferation rescued in part by chromosome 3 duplication. This study defines genomic and phenotypic correlates of cancer aneuploidy and provides an experimental approach to study chromosome arm aneuploidy. Analyzing >10,000 human cancers, Taylor et al. show that aneuploidy is correlated with somatic mutation rate, expression of proliferation genes, and decreased leukocyte infiltration. Loss of chromosome arm 3p is common in squamous cancers, but deletion of chromosome 3p reduces cell proliferation in vitro.
Published: 2018

22. A Pan-Cancer Analysis Reveals High-Frequency Genetic Alterations in Mediators of Signaling by the TGF-β Superfamily

Author: Anil Korkut, Sobia Zaidi, Rupa S. Kanchi, Shuyun Rao, Nancy R. Gough, Andre Schultz, Xubin Li, Philip L. Lorenzi, Ashton C. Berger, Gordon Robertson, Lawrence N. Kwong, Mike Datto, Jason Roszik, Shiyun Ling, Visweswaran Ravikumar, Ganiraju Manyam, Arvind Rao, Simon Shelley, Yuexin Liu, Zhenlin Ju, Donna Hansel, Guillermo de Velasco, Arjun Pennathur, Jesper B. Andersen, Colm J. O'Rourke, Kazufumi Ohshiro, Wilma Jogunoori, Bao-Ngoc Nguyen, Shulin Li, Hatice U. Osmanbeyoglu, Jaffer A. Ajani, Sendurai A. Mani, Andres Houseman, Maciej Wiznerowicz, Jian Chen, Shoujun Gu, Wencai Ma, Jiexin Zhang, Pan Tong, Andrew D. Cherniack, Chuxia Deng, Linda Resar, John N. Weinstein, Lopa Mishra, Rehan Akbani, Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, Gad Getz, David I. Heiman, Jaegil Kim, Michael S. Lawrence, Pei Lin, Sam Meier, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Michael Miller, Sheila Reynolds, Ilya Shmulevich, Vesteinn Thorsson, Wei Zhang, Bradley M. Broom, Apurva M. Hegde, Jun Li, Han Liang, Wenbin Liu, Yiling Lu, Gordon B. Mills, Kwok-Shing Ng, Michael Ryan, Jing Wang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K. Chatila, Ino de Bruijn, Jianjiong Gao, Benjamin E. Gross, Zachary J. Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G. Nissan, Angelica Ochoa, Sarah M. Phillips, Ed Reznik, Francisco Sanchez-Vega, Chris Sander, Nikolaus Schultz, Robert Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, Joshua M. Stuart, Christopher K. Wong, Christina Yau, D. Neil Hayes, Joel S. Parker, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, A. Gordon Robertson, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Rameen Beroukhim, Carrie Cibulskis, Stacey B. Gabriel, Galen F. Gao, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju S. Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz S. Bootwalla, Phillip H. Lai, Dennis T. Maglinte, David J. Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Cheng Fan, Katherine A. Hoadley, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Amy H. Perou, Charles M. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Huihui Fan, Toshinori Hinoue, Peter W. Laird, Hui Shen, Wanding Zhou, Michelle Bellair, Kyle Chang, Kyle Covington, Chad J. Creighton, Huyen Dinh, HarshaVardhan Doddapaneni, Lawrence A. Donehower, Jennifer Drummond, Richard A. Gibbs, Robert Glenn, Walker Hale, Yi Han, Jianhong Hu, Viktoriya Korchina, Sandra Lee, Lora Lewis, Wei Li, Xiuping Liu, Margaret Morgan, Donna Morton, Donna Muzny, Jireh Santibanez, Margi Sheth, Eve Shinbrot, Linghua Wang, Min Wang, David A. Wheeler, Liu Xi, Fengmei Zhao, Julian Hess, Elizabeth L. Appelbaum, Matthew Bailey, Matthew G. Cordes, Li Ding, Catrina C. Fronick, Lucinda A. Fulton, Robert S. Fulton, Cyriac Kandoth, Elaine R. Mardis, Michael D. McLellan, Christopher A. Miller, Heather K. Schmidt, Richard K. Wilson, Daniel Crain, Erin Curley, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Mark Sherman, Eric Thompson, Peggy Yena, Jay Bowen, Julie M. Gastier-Foster, Mark Gerken, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Niall Corcoran, Tony Costello, Christopher Hovens, Andre L. Carvalho, Ana C. de Carvalho, José H. Fregnani, Adhemar Longatto-Filho, Rui M. Reis, Cristovam Scapulatempo-Neto, Henrique C.S. Silveira, Daniel O. Vidal, Andrew Burnette, Jennifer Eschbacher, Beth Hermes, Ardene Noss, Rosy Singh, Matthew L. Anderson, Patricia D. Castro, Michael Ittmann, David Huntsman, Bernard Kohl, Xuan Le, Richard Thorp, Chris Andry, Elizabeth R. Duffy, Vladimir Lyadov, Oxana Paklina, Galiya Setdikova, Alexey Shabunin, Mikhail Tavobilov, Christopher McPherson, Ronald Warnick, Ross Berkowitz, Daniel Cramer, Colleen Feltmate, Neil Horowitz, Adam Kibel, Michael Muto, Chandrajit P. Raut, Andrei Malykh, Jill S. Barnholtz-Sloan, Wendi Barrett, Karen Devine, Jordonna Fulop, Quinn T. Ostrom, Kristen Shimmel, Yingli Wolinsky, Andrew E. Sloan, Agostino De Rose, Felice Giuliante, Marc Goodman, Beth Y. Karlan, Curt H. Hagedorn, John Eckman, Jodi Harr, Jerome Myers, Kelinda Tucker, Leigh Anne Zach, Brenda Deyarmin, Hai Hu, Leonid Kvecher, Caroline Larson, Richard J. Mural, Stella Somiari, Ales Vicha, Tomas Zelinka, Joseph Bennett, Mary Iacocca, Brenda Rabeno, Patricia Swanson, Mathieu Latour, Louis Lacombe, Bernard Têtu, Alain Bergeron, Mary McGraw, Susan M. Staugaitis, John Chabot, Hanina Hibshoosh, Antonia Sepulveda, Tao Su, Timothy Wang, Olga Potapova, Olga Voronina, Laurence Desjardins, Odette Mariani, Sergio Roman-Roman, Xavier Sastre, Marc-Henri Stern, Feixiong Cheng, Sabina Signoretti, Andrew Berchuck, Darell Bigner, Eric Lipp, Jeffrey Marks, Shannon McCall, Roger McLendon, Angeles Secord, Alexis Sharp, Madhusmita Behera, Daniel J. Brat, Amy Chen, Keith Delman, Seth Force, Fadlo Khuri, Kelly Magliocca, Shishir Maithel, Jeffrey J. Olson, Taofeek Owonikoko, Alan Pickens, Suresh Ramalingam, Dong M. Shin, Gabriel Sica, Erwin G. Van Meir, Hongzheng Zhang, Wil Eijckenboom, Ad Gillis, Esther Korpershoek, Leendert Looijenga, Wolter Oosterhuis, Hans Stoop, Kim E. van Kessel, Ellen C. Zwarthoff, Chiara Calatozzolo, Lucia Cuppini, Stefania Cuzzubbo, Francesco DiMeco, Gaetano Finocchiaro, Luca Mattei, Alessandro Perin, Bianca Pollo, Chu Chen, John Houck, Pawadee Lohavanichbutr, Arndt Hartmann, Christine Stoehr, Robert Stoehr, Helge Taubert, Sven Wach, Bernd Wullich, Witold Kycler, Dawid Murawa, Ki Chung, W. Jeffrey Edenfield, Julie Martin, Eric Baudin, Glenn Bubley, Raphael Bueno, Assunta De Rienzo, William G. Richards, Steven Kalkanis, Tom Mikkelsen, Houtan Noushmehr, Lisa Scarpace, Nicolas Girard, Marta Aymerich, Elias Campo, Eva Giné, Armando López Guillermo, Nguyen Van Bang, Phan Thi Hanh, Bui Duc Phu, Yufang Tang, Howard Colman, Kimberley Evason, Peter R. Dottino, John A. Martignetti, Hani Gabra, Hartmut Juhl, Teniola Akeredolu, Serghei Stepa, Dave Hoon, Keunsoo Ahn, Koo Jeong Kang, Felix Beuschlein, Anne Breggia, Michael Birrer, Debra Bell, Mitesh Borad, Alan H. Bryce, Erik Castle, Vishal Chandan, John Cheville, John A. Copland, Michael Farnell, Thomas Flotte, Nasra Giama, Thai Ho, Michael Kendrick, Jean-Pierre Kocher, Karla Kopp, Catherine Moser, David Nagorney, Daniel O’Brien, Brian Patrick O’Neill, Tushar Patel, Gloria Petersen, Florencia Que, Michael Rivera, Lewis Roberts, Robert Smallridge, Thomas Smyrk, Melissa Stanton, R. Houston Thompson, Michael Torbenson, Ju Dong Yang, Lizhi Zhang, Fadi Brimo, Ana Maria Angulo Gonzalez, Carmen Behrens, Jolanta Bondaruk, Russell Broaddus, Bogdan Czerniak, Bita Esmaeli, Junya Fujimoto, Jeffrey Gershenwald, Charles Guo, Alexander J. Lazar, Christopher Logothetis, Funda Meric-Bernstam, Cesar Moran, Lois Ramondetta, David Rice, Anil Sood, Pheroze Tamboli, Timothy Thompson, Patricia Troncoso, Anne Tsao, Ignacio Wistuba, Candace Carter, Lauren Haydu, Peter Hersey, Valerie Jakrot, Hojabr Kakavand, Richard Kefford, Kenneth Lee, Georgina Long, Graham Mann, Michael Quinn, Robyn Saw, Richard Scolyer, Kerwin Shannon, Andrew Spillane, Jonathan Stretch, Maria Synott, John Thompson, James Wilmott, Hikmat Al-Ahmadie, Timothy A. Chan, Ronald Ghossein, Anuradha Gopalan, Douglas A. Levine, Victor Reuter, Samuel Singer, Bhuvanesh Singh, Nguyen Viet Tien, Thomas Broudy, Cyrus Mirsaidi, Praveen Nair, Paul Drwiega, Judy Miller, Jennifer Smith, Howard Zaren, Joong-Won Park, Nguyen Phi Hung, Electron Kebebew, W. Marston Linehan, Adam R. Metwalli, Karel Pacak, Peter A. Pinto, Mark Schiffman, Laura S. Schmidt, Cathy D. Vocke, Nicolas Wentzensen, Robert Worrell, Hannah Yang, Marc Moncrieff, Chandra Goparaju, Jonathan Melamed, Harvey Pass, Natalia Botnariuc, Irina Caraman, Mircea Cernat, Inga Chemencedji, Adrian Clipca, Serghei Doruc, Ghenadie Gorincioi, Sergiu Mura, Maria Pirtac, Irina Stancul, Diana Tcaciuc, Monique Albert, Iakovina Alexopoulou, Angel Arnaout, John Bartlett, Jay Engel, Sebastien Gilbert, Jeremy Parfitt, Harman Sekhon, George Thomas, Doris M. Rassl, Robert C. Rintoul, Carlo Bifulco, Raina Tamakawa, Walter Urba, Nicholas Hayward, Henri Timmers, Anna Antenucci, Francesco Facciolo, Gianluca Grazi, Mirella Marino, Roberta Merola, Ronald de Krijger, Anne-Paule Gimenez-Roqueplo, Alain Piché, Simone Chevalier, Ginette McKercher, Kivanc Birsoy, Gene Barnett, Cathy Brewer, Carol Farver, Theresa Naska, Nathan A. Pennell, Daniel Raymond, Cathy Schilero, Kathy Smolenski, Felicia Williams, Carl Morrison, Jeffrey A. Borgia, Michael J. Liptay, Mark Pool, Christopher W. 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Aredes, Armaz Mariamidze, Korkut A., Zaidi S., Kanchi R.S., Rao S., Gough N.R., Schultz A., Li X., Lorenzi P.L., Berger A.C., Robertson G., Kwong L.N., Datto M., Roszik J., Ling S., Ravikumar V., Manyam G., Rao A., Shelley S., Liu Y., Ju Z., Hansel D., de Velasco G., Pennathur A., Andersen J.B., O'Rourke C.J., Ohshiro K., Jogunoori W., Nguyen B.-N., Li S., Osmanbeyoglu H.U., Ajani J.A., Mani S.A., Houseman A., Wiznerowicz M., Chen J., Gu S., Ma W., Zhang J., Tong P., Cherniack A.D., Deng C., Resar L., Caesar-Johnson S.J., Demchok J.A., Felau I., Kasapi M., Ferguson M.L., Hutter C.M., Sofia H.J., Tarnuzzer R., Wang Z., Yang L., Zenklusen J.C., Zhang J.J., Chudamani S., Liu J., Lolla L., Naresh R., Pihl T., Sun Q., Wan Y., Wu Y., Cho J., DeFreitas T., Frazer S., Gehlenborg N., Getz G., Heiman D.I., Kim J., Lawrence M.S., Lin P., Meier S., Noble M.S., Saksena G., Voet D., Zhang H., Bernard B., Chambwe N., Dhankani V., Knijnenburg T., Kramer R., Leinonen K., Miller M., Reynolds S., 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L., Tetu B., Bergeron A., McGraw M., Staugaitis S.M., Chabot J., Hibshoosh H., Sepulveda A., Su T., Wang T., Potapova O., Voronina O., Desjardins L., Mariani O., Roman-Roman S., Sastre X., Stern M.-H., Cheng F., Signoretti S., Berchuck A., Bigner D., Lipp E., Marks J., McCall S., McLendon R., Secord A., Sharp A., Behera M., Brat D.J., Chen A., Delman K., Force S., Khuri F., Magliocca K., Maithel S., Olson J.J., Owonikoko T., Pickens A., Ramalingam S., Shin D.M., Sica G., Van Meir E.G., Eijckenboom W., Gillis A., Korpershoek E., Looijenga L., Oosterhuis W., Stoop H., van Kessel K.E., Zwarthoff E.C., Calatozzolo C., Cuppini L., Cuzzubbo S., DiMeco F., Finocchiaro G., Mattei L., Perin A., Pollo B., Chen C., Houck J., Lohavanichbutr P., Hartmann A., Stoehr C., Stoehr R., Taubert H., Wach S., Wullich B., Kycler W., Murawa D., Chung K., Edenfield W.J., Martin J., Baudin E., Bubley G., Bueno R., De Rienzo A., Richards W.G., Kalkanis S., Mikkelsen T., Noushmehr H., Scarpace L., Girard N., 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R., Shannon K., Spillane A., Stretch J., Synott M., Thompson J., Wilmott J., Al-Ahmadie H., Chan T.A., Ghossein R., Gopalan A., Levine D.A., Reuter V., Singer S., Singh B., Tien N.V., Broudy T., Mirsaidi C., Nair P., Drwiega P., Miller J., Smith J., Zaren H., Park J.-W., Hung N.P., Kebebew E., Linehan W.M., Metwalli A.R., Pacak K., Pinto P.A., Schiffman M., Schmidt L.S., Vocke C.D., Wentzensen N., Worrell R., Yang H., Moncrieff M., Goparaju C., Melamed J., Pass H., Botnariuc N., Caraman I., Cernat M., Chemencedji I., Clipca A., Doruc S., Gorincioi G., Mura S., Pirtac M., Stancul I., Tcaciuc D., Albert M., Alexopoulou I., Arnaout A., Bartlett J., Engel J., Gilbert S., Parfitt J., Sekhon H., Thomas G., Rassl D.M., Rintoul R.C., Bifulco C., Tamakawa R., Urba W., Hayward N., Timmers H., Antenucci A., Facciolo F., Grazi G., Marino M., Merola R., de Krijger R., Gimenez-Roqueplo A.-P., Piche A., Chevalier S., McKercher G., Birsoy K., Barnett G., Brewer C., Farver C., Naska T., Pennell N.A., 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S., Steele R., Jimeno A., Carey F., Forgie I., Mannelli M., Carney M., Hernandez B., Campos B., Herold-Mende C., Jungk C., Unterberg A., von Deimling A., Bossler A., Galbraith J., Jacobus L., Knudson M., Knutson T., Ma D., Milhem M., Sigmund R., Godwin A.K., Madan R., Rosenthal H.G., Adebamowo C., Adebamowo S.N., Boussioutas A., Beer D., Giordano T., Mes-Masson A.-M., Saad F., Bocklage T., Landrum L., Mannel R., Moore K., Moxley K., Postier R., Walker J., Zuna R., Feldman M., Valdivieso F., Dhir R., Luketich J., Mora Pinero E.M., Quintero-Aguilo M., Carlotti C.G., Dos Santos J.S., Kemp R., Sankarankuty A., Tirapelli D., Catto J., Agnew K., Swisher E., Creaney J., Robinson B., Shelley C.S., Godwin E.M., Kendall S., Shipman C., Bradford C., Carey T., Haddad A., Moyer J., Peterson L., Prince M., Rozek L., Wolf G., Bowman R., Fong K.M., Yang I., Korst R., Rathmell W.K., Fantacone-Campbell J.L., Hooke J.A., Kovatich A.J., Shriver C.D., DiPersio J., Drake B., Govindan R., Heath S., Ley T., Van Tine B., Westervelt P., Rubin M.A., Lee J.I., Aredes N.D., Mariamidze A., Mishra L., SAIC-F-Frederick, Inc, and Leidos Biomedical Research, Inc.
Subjects: 0301 basic medicine, Receptor, Transforming Growth Factor-beta Type I, Cancer Genome Atlas Research Network, Smad Proteins, Bone Morphogenetic Protein 5, Pan-Cancer, Mutation Rate, Transforming Growth Factor beta, Neoplasms, LS2_1, 2.1 Biological and endogenous factors, LS4_6, Aetiology, DNA methylation, biology, microRNA, Smad Protein, Transforming Growth Factor-beta Type I, TGF-β pathway, Signal transduction, mutation hotspot, transcription, Receptor, Biotechnology, Human, Signal Transduction, TGF-β, Histology, The Cancer Genome Atlas, TCGA, TGF-?, TGF-? pathway, cancer, Article, Pathology and Forensic Medicine, NO, 03 medical and health sciences, HMGA2, Genetics, Humans, Gene, Human Genome, Cell Biology, Transforming growth factor beta, DNA Methylation, BMPR2, MicroRNAs, 030104 developmental biology, biology.protein, Cancer research, Neoplasm, Human genome, Biochemistry and Cell Biology, The Cancer Genome Atla
Abstract: We present an integromic analysis of gene alterations that modulate transforming growth factor β (TGF-β)-Smad-mediated signaling in 9,125 tumor samples across 33 cancer types in The Cancer Genome Atlas (TCGA). Focusing on genes that encode mediators and regulators of TGF-β signaling, we found at least one genomic alteration (mutation, homozygous deletion, or amplification) in 39% of samples, with highest frequencies in gastrointestinal cancers. We identified mutation hotspots in genes that encode TGF-β ligands (BMP5), receptors (TGFBR2, AVCR2A, and BMPR2), and Smads (SMAD2 and SMAD4). Alterations in the TGF-β superfamily correlated positively with expression of metastasis-associated genes and with decreased survival. Correlation analyses showed the contributions of mutation, amplification, deletion, DNA methylation, and miRNA expression to transcriptional activity of TGF-β signaling in each cancer type. This study provides a broad molecular perspective relevant for future functional and therapeutic studies of the diverse cancer pathways mediated by the TGF-β superfamily. To date, there are no studies of the TGF-β superfamily of signaling pathways across multiple cancers. This study represents a key starting point for unraveling the role of this complex superfamily in 33 divergent cancer types from over 9,000 patients.
Published: 2018

23. Pathogenic Germline Variants in 10,389 Adult Cancers

Author: Kuan-lin Huang, R. Jay Mashl, Yige Wu, Deborah I. Ritter, Jiayin Wang, Clara Oh, Marta Paczkowska, Sheila Reynolds, Matthew A. Wyczalkowski, Ninad Oak, Adam D. Scott, Michal Krassowski, Andrew D. Cherniack, Kathleen E. Houlahan, Reyka Jayasinghe, Liang-Bo Wang, Daniel Cui Zhou, Di Liu, Song Cao, Young Won Kim, Amanda Koire, Joshua F. McMichael, Vishwanathan Hucthagowder, Tae-Beom Kim, Abigail Hahn, Chen Wang, Michael D. McLellan, Fahd Al-Mulla, Kimberly J. Johnson, Olivier Lichtarge, Paul C. Boutros, Benjamin Raphael, Alexander J. Lazar, Wei Zhang, Michael C. Wendl, Ramaswamy Govindan, Sanjay Jain, David Wheeler, Shashikant Kulkarni, John F. Dipersio, Jüri Reimand, Funda Meric-Bernstam, Ken Chen, Ilya Shmulevich, Sharon E. Plon, Feng Chen, Li Ding, Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, Gad Getz, David I. Heiman, Jaegil Kim, Michael S. Lawrence, Pei Lin, Sam Meier, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Yuexin Liu, Michael Miller, Vesteinn Thorsson, Rehan Akbani, Bradley M. Broom, Apurva M. Hegde, Zhenlin Ju, Rupa S. Kanchi, Anil Korkut, Jun Li, Han Liang, Shiyun Ling, Wenbin Liu, Yiling Lu, Gordon B. Mills, Kwok-Shing Ng, Arvind Rao, Michael Ryan, Jing Wang, John N. Weinstein, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K. Chatila, Ino de Bruijn, Jianjiong Gao, Benjamin E. Gross, Zachary J. Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G. Nissan, Angelica Ochoa, Sarah M. Phillips, Ed Reznik, Francisco Sanchez-Vega, Chris Sander, Nikolaus Schultz, Robert Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, Joshua M. Stuart, Christopher K. Wong, Christina Yau, D. Neil Hayes, Joel S. Parker, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, A. Gordon Robertson, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Ashton C. Berger, Rameen Beroukhim, Carrie Cibulskis, Stacey B. Gabriel, Galen F. Gao, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju S. Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz S. Bootwalla, Phillip H. 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Fulton, Robert S. Fulton, Cyriac Kandoth, Elaine R. Mardis, Christopher A. Miller, Heather K. Schmidt, Richard K. Wilson, Daniel Crain, Erin Curley, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Mark Sherman, Eric Thompson, Peggy Yena, Jay Bowen, Julie M. Gastier-Foster, Mark Gerken, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Niall Corcoran, Tony Costello, Christopher Hovens, Andre L. Carvalho, Ana C. de Carvalho, José H. Fregnani, Adhemar Longatto-Filho, Rui M. Reis, Cristovam Scapulatempo-Neto, Henrique C.S. Silveira, Daniel O. Vidal, Andrew Burnette, Jennifer Eschbacher, Beth Hermes, Ardene Noss, Rosy Singh, Matthew L. Anderson, Patricia D. Castro, Michael Ittmann, David Huntsman, Bernard Kohl, Xuan Le, Richard Thorp, Chris Andry, Elizabeth R. 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Schmidt, Cathy D. Vocke, Nicolas Wentzensen, Robert Worrell, Hannah Yang, Marc Moncrieff, Chandra Goparaju, Jonathan Melamed, Harvey Pass, Natalia Botnariuc, Irina Caraman, Mircea Cernat, Inga Chemencedji, Adrian Clipca, Serghei Doruc, Ghenadie Gorincioi, Sergiu Mura, Maria Pirtac, Irina Stancul, Diana Tcaciuc, Monique Albert, Iakovina Alexopoulou, Angel Arnaout, John Bartlett, Jay Engel, Sebastien Gilbert, Jeremy Parfitt, Harman Sekhon, George Thomas, Doris M. Rassl, Robert C. Rintoul, Carlo Bifulco, Raina Tamakawa, Walter Urba, Nicholas Hayward, Henri Timmers, Anna Antenucci, Francesco Facciolo, Gianluca Grazi, Mirella Marino, Roberta Merola, Ronald de Krijger, Anne-Paule Gimenez-Roqueplo, Alain Piché, Simone Chevalier, Ginette McKercher, Kivanc Birsoy, Gene Barnett, Cathy Brewer, Carol Farver, Theresa Naska, Nathan A. Pennell, Daniel Raymond, Cathy Schilero, Kathy Smolenski, Felicia Williams, Carl Morrison, Jeffrey A. Borgia, Michael J. Liptay, Mark Pool, Christopher W. Seder, Kerstin Junker, Larsson Omberg, Mikhail Dinkin, George Manikhas, Domenico Alvaro, Maria Consiglia Bragazzi, Vincenzo Cardinale, Guido Carpino, Eugenio Gaudio, David Chesla, Sandra Cottingham, Michael Dubina, Fedor Moiseenko, Renumathy Dhanasekaran, Karl-Friedrich Becker, Klaus-Peter Janssen, Julia Slotta-Huspenina, Mohamed H. Abdel-Rahman, Dina Aziz, Sue Bell, Colleen M. Cebulla, Amy Davis, Rebecca Duell, J. Bradley Elder, Joe Hilty, Bahavna Kumar, James Lang, Norman L. Lehman, Randy Mandt, Phuong Nguyen, Robert Pilarski, Karan Rai, Lynn Schoenfield, Kelly Senecal, Paul Wakely, Paul Hansen, Ronald Lechan, James Powers, Arthur Tischler, William E. Grizzle, Katherine C. Sexton, Alison Kastl, Joel Henderson, Sima Porten, Jens Waldmann, Martin Fassnacht, Sylvia L. Asa, Dirk Schadendorf, Marta Couce, Markus Graefen, Hartwig Huland, Guido Sauter, Thorsten Schlomm, Ronald Simon, Pierre Tennstedt, Oluwole Olabode, Mark Nelson, Oliver Bathe, Peter R. Carroll, June M. Chan, Philip Disaia, Pat Glenn, Robin K. Kelley, Charles N. Landen, Joanna Phillips, Michael Prados, Jeffry Simko, Karen Smith-McCune, Scott VandenBerg, Kevin Roggin, Ashley Fehrenbach, Ady Kendler, Suzanne Sifri, Ruth Steele, Antonio Jimeno, Francis Carey, Ian Forgie, Massimo Mannelli, Michael Carney, Brenda Hernandez, Benito Campos, Christel Herold-Mende, Christin Jungk, Andreas Unterberg, Andreas von Deimling, Aaron Bossler, Joseph Galbraith, Laura Jacobus, Michael Knudson, Tina Knutson, Deqin Ma, Mohammed Milhem, Rita Sigmund, Andrew K. Godwin, Rashna Madan, Howard G. Rosenthal, Clement Adebamowo, Sally N. Adebamowo, Alex Boussioutas, David Beer, Thomas Giordano, Anne-Marie Mes-Masson, Fred Saad, Therese Bocklage, Lisa Landrum, Robert Mannel, Kathleen Moore, Katherine Moxley, Russel Postier, Joan Walker, Rosemary Zuna, Michael Feldman, Federico Valdivieso, Rajiv Dhir, James Luketich, Edna M. Mora Pinero, Mario Quintero-Aguilo, Carlos Gilberto Carlotti, Jose Sebastião Dos Santos, Rafael Kemp, Ajith Sankarankuty, Daniela Tirapelli, James Catto, Kathy Agnew, Elizabeth Swisher, Jenette Creaney, Bruce Robinson, Carl Simon Shelley, Eryn M. Godwin, Sara Kendall, Cassaundra Shipman, Carol Bradford, Thomas Carey, Andrea Haddad, Jeffey Moyer, Lisa Peterson, Mark Prince, Laura Rozek, Gregory Wolf, Rayleen Bowman, Kwun M. Fong, Ian Yang, Robert Korst, W. Kimryn Rathmell, J. Leigh Fantacone-Campbell, Jeffrey A. Hooke, Albert J. Kovatich, Craig D. Shriver, John DiPersio, Bettina Drake, Sharon Heath, Timothy Ley, Brian Van Tine, Peter Westervelt, Mark A. Rubin, Jung Il Lee, Natália D. 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J.M., Gerken M., Leraas K.M., Lichtenberg T.M., Ramirez N.C., Wise L., Zmuda E., Corcoran N., Costello T., Hovens C., Carvalho A.L., de Carvalho A.C., Fregnani J.H., Longatto-Filho A., Reis R.M., Scapulatempo-Neto C., Silveira H.C.S., Vidal D.O., Burnette A., Eschbacher J., Hermes B., Noss A., Singh R., Anderson M.L., Castro P.D., Ittmann M., Huntsman D., Kohl B., Le X., Thorp R., Andry C., Duffy E.R., Lyadov V., Paklina O., Setdikova G., Shabunin A., Tavobilov M., McPherson C., Warnick R., Berkowitz R., Cramer D., Feltmate C., Horowitz N., Kibel A., Muto M., Raut C.P., Malykh A., Barnholtz-Sloan J.S., Barrett W., Devine K., Fulop J., Ostrom Q.T., Shimmel K., Wolinsky Y., Sloan A.E., De Rose A., Giuliante F., Goodman M., Karlan B.Y., Hagedorn C.H., Eckman J., Harr J., Myers J., Tucker K., Zach L.A., Deyarmin B., Hu H., Kvecher L., Larson C., Mural R.J., Somiari S., Vicha A., Zelinka T., Bennett J., Iacocca M., Rabeno B., Swanson P., Latour M., Lacombe L., Tetu B., Bergeron A., McGraw M., Staugaitis S.M., Chabot J., Hibshoosh H., Sepulveda A., Su T., Wang T., Potapova O., Voronina O., Desjardins L., Mariani O., Roman-Roman S., Sastre X., Stern M.-H., Cheng F., Signoretti S., Berchuck A., Bigner D., Lipp E., Marks J., McCall S., McLendon R., Secord A., Sharp A., Behera M., Brat D.J., Chen A., Delman K., Force S., Khuri F., Magliocca K., Maithel S., Olson J.J., Owonikoko T., Pickens A., Ramalingam S., Shin D.M., Sica G., Van Meir E.G., Eijckenboom W., Gillis A., Korpershoek E., Looijenga L., Oosterhuis W., Stoop H., van Kessel K.E., Zwarthoff E.C., Calatozzolo C., Cuppini L., Cuzzubbo S., DiMeco F., Finocchiaro G., Mattei L., Perin A., Pollo B., Chen C., Houck J., Lohavanichbutr P., Hartmann A., Stoehr C., Stoehr R., Taubert H., Wach S., Wullich B., Kycler W., Murawa D., Wiznerowicz M., Chung K., Edenfield W.J., Martin J., Baudin E., Bubley G., Bueno R., De Rienzo A., Richards W.G., Kalkanis S., Mikkelsen T., Noushmehr H., Scarpace L., Girard N., Aymerich M., Campo 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K., Spillane A., Stretch J., Synott M., Thompson J., Wilmott J., Al-Ahmadie H., Chan T.A., Ghossein R., Gopalan A., Levine D.A., Reuter V., Singer S., Singh B., Tien N.V., Broudy T., Mirsaidi C., Nair P., Drwiega P., Miller J., Smith J., Zaren H., Park J.-W., Hung N.P., Kebebew E., Linehan W.M., Metwalli A.R., Pacak K., Pinto P.A., Schiffman M., Schmidt L.S., Vocke C.D., Wentzensen N., Worrell R., Yang H., Moncrieff M., Goparaju C., Melamed J., Pass H., Botnariuc N., Caraman I., Cernat M., Chemencedji I., Clipca A., Doruc S., Gorincioi G., Mura S., Pirtac M., Stancul I., Tcaciuc D., Albert M., Alexopoulou I., Arnaout A., Bartlett J., Engel J., Gilbert S., Parfitt J., Sekhon H., Thomas G., Rassl D.M., Rintoul R.C., Bifulco C., Tamakawa R., Urba W., Hayward N., Timmers H., Antenucci A., Facciolo F., Grazi G., Marino M., Merola R., de Krijger R., Gimenez-Roqueplo A.-P., Piche A., Chevalier S., McKercher G., Birsoy K., Barnett G., Brewer C., Farver C., Naska T., Pennell N.A., Raymond D., Schilero C., Smolenski K., Williams F., Morrison C., Borgia J.A., Liptay M.J., Pool M., Seder C.W., Junker K., Omberg L., Dinkin M., Manikhas G., Alvaro D., Bragazzi M.C., Cardinale V., Carpino G., Gaudio E., Chesla D., Cottingham S., Dubina M., Moiseenko F., Dhanasekaran R., Becker K.-F., Janssen K.-P., Slotta-Huspenina J., Abdel-Rahman M.H., Aziz D., Bell S., Cebulla C.M., Davis A., Duell R., Elder J.B., Hilty J., Kumar B., Lang J., Lehman N.L., Mandt R., Nguyen P., Pilarski R., Rai K., Schoenfield L., Senecal K., Wakely P., Hansen P., Lechan R., Powers J., Tischler A., Grizzle W.E., Sexton K.C., Kastl A., Henderson J., Porten S., Waldmann J., Fassnacht M., Asa S.L., Schadendorf D., Couce M., Graefen M., Huland H., Sauter G., Schlomm T., Simon R., Tennstedt P., Olabode O., Nelson M., Bathe O., Carroll P.R., Chan J.M., Disaia P., Glenn P., Kelley R.K., Landen C.N., Phillips J., Prados M., Simko J., Smith-McCune K., VandenBerg S., Roggin K., Fehrenbach A., Kendler A., Sifri S., Steele R., Jimeno A., Carey F., Forgie I., Mannelli M., Carney M., Hernandez B., Campos B., Herold-Mende C., Jungk C., Unterberg A., von Deimling A., Bossler A., Galbraith J., Jacobus L., Knudson M., Knutson T., Ma D., Milhem M., Sigmund R., Godwin A.K., Madan R., Rosenthal H.G., Adebamowo C., Adebamowo S.N., Boussioutas A., Beer D., Giordano T., Mes-Masson A.-M., Saad F., Bocklage T., Landrum L., Mannel R., Moore K., Moxley K., Postier R., Walker J., Zuna R., Feldman M., Valdivieso F., Dhir R., Luketich J., Pinero E.M.M., Quintero-Aguilo M., Carlotti C.G., Dos Santos J.S., Kemp R., Sankarankuty A., Tirapelli D., Catto J., Agnew K., Swisher E., Creaney J., Robinson B., Shelley C.S., Godwin E.M., Kendall S., Shipman C., Bradford C., Carey T., Haddad A., Moyer J., Peterson L., Prince M., Rozek L., Wolf G., Bowman R., Fong K.M., Yang I., Korst R., Rathmell W.K., Fantacone-Campbell J.L., Hooke J.A., Kovatich A.J., Shriver C.D., DiPersio J., Drake B., Govindan R., Heath S., Ley T., Van Tine B., Westervelt P., Rubin M.A., Lee J.I., Aredes N.D., Mariamidze A., Lichtarge O., Boutros P.C., Raphael B., Wendl M.C., Jain S., Wheeler D., Kulkarni S., Dipersio J.F., Reimand J., Chen K., Plon S.E., and Chen F.
Subjects: 0301 basic medicine, SDHA, Loss of Heterozygosity, Cancer Genome Atlas Research Network, GUIDELINES, Germline, Loss of heterozygosity, Gene Frequency, Neoplasms, Genotype, Databases, Genetic, LS2_1, LS4_6, LOH, 610 Medicine & health, 11 Medical and Health Sciences, DNA Copy Number Variation, RISK, Genetics, SITES, medicine.diagnostic_test, Proto-Oncogene Proteins c-met, germline and somatic genomes, Life Sciences & Biomedicine, Human, Biochemistry & Molecular Biology, DNA Copy Number Variations, PALB2, Mutation, Missense, cancer predisposition, Biology, GENOMAS, Polymorphism, Single Nucleotide, Germ Cell, General Biochemistry, Genetics and Molecular Biology, Article, NO, 03 medical and health sciences, Germline mutation, variant pathogenicity, KINASE, medicine, Humans, Genetic Predisposition to Disease, germline and somatic genome, Allele frequency, Germ-Line Mutation, Genetic testing, Science & Technology, MUTATIONS, Tumor Suppressor Proteins, Proto-Oncogene Proteins c-ret, Cell Biology, 06 Biological Sciences, BRCA1, 030104 developmental biology, Germ Cells, DISCOVERY, Neoplasm, GENOMICS, Gene Deletion, Developmental Biology
Abstract: We conducted the largest investigation of predisposition variants in cancer to date, discovering 853 pathogenic or likely pathogenic variants in 8% of 10,389 cases from 33 cancer types. Twenty-one genes showed single or cross-cancer associations, including novel associations of SDHA in melanoma and PALB2 in stomach adenocarcinoma. The 659 predisposition variants and 18 additional large deletions in tumor suppressors, including ATM, BRCA1, and NF1, showed low gene expression and frequent (43%) loss of heterozygosity or biallelic two-hit events. We also discovered 33 such variants in oncogenes, including missenses in MET, RET, and PTPN11 associated with high gene expression. We nominated 47 additional predisposition variants from prioritized VUSs supported by multiple evidences involving case-control frequency, loss of heterozygosity, expression effect, and co-localization with mutations and modified residues. Our integrative approach links rare predisposition variants to functional consequences, informing future guidelines of variant classification and germline genetic testing in cancer. A pan-cancer analysis identifies hundreds of predisposing germline variants.
Published: 2018

24. Comprehensive Analysis of Alternative Splicing Across Tumors from 8,705 Patients

Author: André Kahles, Kjong-Van Lehmann, Nora C. Toussaint, Matthias Hüser, Stefan G. Stark, Timo Sachsenberg, Oliver Stegle, Oliver Kohlbacher, Chris Sander, Gunnar Rätsch, Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, Gad Getz, David I. Heiman, Jaegil Kim, Michael S. Lawrence, Pei Lin, Sam Meier, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Yuexin Liu, Michael Miller, Sheila Reynolds, Ilya Shmulevich, Vesteinn Thorsson, Wei Zhang, Rehan Akbani, Bradley M. Broom, Apurva M. Hegde, Zhenlin Ju, Rupa S. Kanchi, Anil Korkut, Jun Li, Han Liang, Shiyun Ling, Wenbin Liu, Yiling Lu, Gordon B. Mills, Kwok-Shing Ng, Arvind Rao, Michael Ryan, Jing Wang, John N. Weinstein, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K. Chatila, Ino de Bruijn, Jianjiong Gao, Benjamin E. Gross, Zachary J. Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G. Nissan, Angelica Ochoa, Sarah M. Phillips, Ed Reznik, Francisco Sanchez-Vega, Nikolaus Schultz, Robert Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, Joshua M. Stuart, Christopher K. Wong, Christina Yau, D. Neil Hayes, Joel S. Parker, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, A. Gordon Robertson, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Ashton C. Berger, Rameen Beroukhim, Andrew D. Cherniack, Carrie Cibulskis, Stacey B. Gabriel, Galen F. Gao, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju S. Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz S. Bootwalla, Phillip H. Lai, Dennis T. Maglinte, David J. Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Cheng Fan, Katherine A. Hoadley, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Amy H. Perou, Charles M. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Huihui Fan, Toshinori Hinoue, Peter W. Laird, Hui Shen, Wanding Zhou, Michelle Bellair, Kyle Chang, Kyle Covington, Chad J. Creighton, Huyen Dinh, HarshaVardhan Doddapaneni, Lawrence A. Donehower, Jennifer Drummond, Richard A. Gibbs, Robert Glenn, Walker Hale, Yi Han, Jianhong Hu, Viktoriya Korchina, Sandra Lee, Lora Lewis, Wei Li, Xiuping Liu, Margaret Morgan, Donna Morton, Donna Muzny, Jireh Santibanez, Margi Sheth, Eve Shinbrot, Linghua Wang, Min Wang, David A. Wheeler, Liu Xi, Fengmei Zhao, Julian Hess, Elizabeth L. Appelbaum, Matthew Bailey, Matthew G. Cordes, Li Ding, Catrina C. Fronick, Lucinda A. Fulton, Robert S. Fulton, Cyriac Kandoth, Elaine R. Mardis, Michael D. McLellan, Christopher A. Miller, Heather K. Schmidt, Richard K. Wilson, Daniel Crain, Erin Curley, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Mark Sherman, Eric Thompson, Peggy Yena, Jay Bowen, Julie M. Gastier-Foster, Mark Gerken, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Niall Corcoran, Tony Costello, Christopher Hovens, Andre L. Carvalho, Ana C. de Carvalho, José H. Fregnani, Adhemar Longatto-Filho, Rui M. Reis, Cristovam Scapulatempo-Neto, Henrique C.S. Silveira, Daniel O. Vidal, Andrew Burnette, Jennifer Eschbacher, Beth Hermes, Ardene Noss, Rosy Singh, Matthew L. Anderson, Patricia D. Castro, Michael Ittmann, David Huntsman, Bernard Kohl, Xuan Le, Richard Thorp, Chris Andry, Elizabeth R. Duffy, Vladimir Lyadov, Oxana Paklina, Galiya Setdikova, Alexey Shabunin, Mikhail Tavobilov, Christopher McPherson, Ronald Warnick, Ross Berkowitz, Daniel Cramer, Colleen Feltmate, Neil Horowitz, Adam Kibel, Michael Muto, Chandrajit P. Raut, Andrei Malykh, Jill S. Barnholtz-Sloan, Wendi Barrett, Karen Devine, Jordonna Fulop, Quinn T. Ostrom, Kristen Shimmel, Yingli Wolinsky, Andrew E. Sloan, Agostino De Rose, Felice Giuliante, Marc Goodman, Beth Y. Karlan, Curt H. Hagedorn, John Eckman, Jodi Harr, Jerome Myers, Kelinda Tucker, Leigh Anne Zach, Brenda Deyarmin, Hai Hu, Leonid Kvecher, Caroline Larson, Richard J. Mural, Stella Somiari, Ales Vicha, Tomas Zelinka, Joseph Bennett, Mary Iacocca, Brenda Rabeno, Patricia Swanson, Mathieu Latour, Louis Lacombe, Bernard Têtu, Alain Bergeron, Mary McGraw, Susan M. Staugaitis, John Chabot, Hanina Hibshoosh, Antonia Sepulveda, Tao Su, Timothy Wang, Olga Potapova, Olga Voronina, Laurence Desjardins, Odette Mariani, Sergio Roman-Roman, Xavier Sastre, Marc-Henri Stern, Feixiong Cheng, Sabina Signoretti, Andrew Berchuck, Darell Bigner, Eric Lipp, Jeffrey Marks, Shannon McCall, Roger McLendon, Angeles Secord, Alexis Sharp, Madhusmita Behera, Daniel J. Brat, Amy Chen, Keith Delman, Seth Force, Fadlo Khuri, Kelly Magliocca, Shishir Maithel, Jeffrey J. Olson, Taofeek Owonikoko, Alan Pickens, Suresh Ramalingam, Dong M. Shin, Gabriel Sica, Erwin G. Van Meir, Hongzheng Zhang, Wil Eijckenboom, Ad Gillis, Esther Korpershoek, Leendert Looijenga, Wolter Oosterhuis, Hans Stoop, Kim E. van Kessel, Ellen C. Zwarthoff, Chiara Calatozzolo, Lucia Cuppini, Stefania Cuzzubbo, Francesco DiMeco, Gaetano Finocchiaro, Luca Mattei, Alessandro Perin, Bianca Pollo, Chu Chen, John Houck, Pawadee Lohavanichbutr, Arndt Hartmann, Christine Stoehr, Robert Stoehr, Helge Taubert, Sven Wach, Bernd Wullich, Witold Kycler, Dawid Murawa, Maciej Wiznerowicz, Ki Chung, W. Jeffrey Edenfield, Julie Martin, Eric Baudin, Glenn Bubley, Raphael Bueno, Assunta De Rienzo, William G. Richards, Steven Kalkanis, Tom Mikkelsen, Houtan Noushmehr, Lisa Scarpace, Nicolas Girard, Marta Aymerich, Elias Campo, Eva Giné, Armando López Guillermo, Nguyen Van Bang, Phan Thi Hanh, Bui Duc Phu, Yufang Tang, Howard Colman, Kimberley Evason, Peter R. Dottino, John A. Martignetti, Hani Gabra, Hartmut Juhl, Teniola Akeredolu, Serghei Stepa, Dave Hoon, Keunsoo Ahn, Koo Jeong Kang, Felix Beuschlein, Anne Breggia, Michael Birrer, Debra Bell, Mitesh Borad, Alan H. Bryce, Erik Castle, Vishal Chandan, John Cheville, John A. Copland, Michael Farnell, Thomas Flotte, Nasra Giama, Thai Ho, Michael Kendrick, Jean-Pierre Kocher, Karla Kopp, Catherine Moser, David Nagorney, Daniel O'Brien, Brian Patrick O'Neill, Tushar Patel, Gloria Petersen, Florencia Que, Michael Rivera, Lewis Roberts, Robert Smallridge, Thomas Smyrk, Melissa Stanton, R. Houston Thompson, Michael Torbenson, Ju Dong Yang, Lizhi Zhang, Fadi Brimo, Jaffer A. Ajani, Ana Maria Angulo Gonzalez, Carmen Behrens, Jolanta Bondaruk, Russell Broaddus, Bogdan Czerniak, Bita Esmaeli, Junya Fujimoto, Jeffrey Gershenwald, Charles Guo, Alexander J. 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Vocke, Nicolas Wentzensen, Robert Worrell, Hannah Yang, Marc Moncrieff, Chandra Goparaju, Jonathan Melamed, Harvey Pass, Natalia Botnariuc, Irina Caraman, Mircea Cernat, Inga Chemencedji, Adrian Clipca, Serghei Doruc, Ghenadie Gorincioi, Sergiu Mura, Maria Pirtac, Irina Stancul, Diana Tcaciuc, Monique Albert, Iakovina Alexopoulou, Angel Arnaout, John Bartlett, Jay Engel, Sebastien Gilbert, Jeremy Parfitt, Harman Sekhon, George Thomas, Doris M. Rassl, Robert C. Rintoul, Carlo Bifulco, Raina Tamakawa, Walter Urba, Nicholas Hayward, Henri Timmers, Anna Antenucci, Francesco Facciolo, Gianluca Grazi, Mirella Marino, Roberta Merola, Ronald de Krijger, Anne-Paule Gimenez-Roqueplo, Alain Piché, Simone Chevalier, Ginette McKercher, Kivanc Birsoy, Gene Barnett, Cathy Brewer, Carol Farver, Theresa Naska, Nathan A. Pennell, Daniel Raymond, Cathy Schilero, Kathy Smolenski, Felicia Williams, Carl Morrison, Jeffrey A. Borgia, Michael J. Liptay, Mark Pool, Christopher W. 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Mora Pinero, Mario Quintero-Aguilo, Carlos Gilberto Carlotti, Jose Sebastião Dos Santos, Rafael Kemp, Ajith Sankarankuty, Daniela Tirapelli, James Catto, Kathy Agnew, Elizabeth Swisher, Jenette Creaney, Bruce Robinson, Carl Simon Shelley, Eryn M. Godwin, Sara Kendall, Cassaundra Shipman, Carol Bradford, Thomas Carey, Andrea Haddad, Jeffey Moyer, Lisa Peterson, Mark Prince, Laura Rozek, Gregory Wolf, Rayleen Bowman, Kwun M. Fong, Ian Yang, Robert Korst, W. Kimryn Rathmell, J. Leigh Fantacone-Campbell, Jeffrey A. Hooke, Albert J. Kovatich, Craig D. Shriver, John DiPersio, Bettina Drake, Ramaswamy Govindan, Sharon Heath, Timothy Ley, Brian Van Tine, Peter Westervelt, Mark A. Rubin, Jung Il Lee, Natália D. 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Subjects: 0301 basic medicine, PTEN, Cancer Research, CPTAC, TCGA Pan-Cancer Atla, Cancer Genome Atlas Research Network, RNA-Seq, VARIANTS, Whole Exome Sequencing, COWDEN-SYNDROME, immunoediting, Ovarian tumor, Neoplasms, LS2_1, LS4_6, 610 Medicine & health, Exome, Exome sequencing, biology, Single Nucleotide, Ovarian Cancer, MS proteomic, Oncology, immunotherapy, Sequence Analysis, Life Sciences & Biomedicine, TCGA Pan-Cancer Atlas, Human, Alternative splicing, Cancer, Tumor-specific splicing, Splicing QTL, Neoantigens, Immunotherapy, Immunoediting, RNA-seq, MS proteomics, TCGA, GTEx, splicing QTL, Oncology and Carcinogenesis, Quantitative Trait Loci, Computational biology, Major histocompatibility complex, Polymorphism, Single Nucleotide, tumor-specific splicing, OVARIAN-CANCER, Article, NO, 03 medical and health sciences, alternative splicing, Rare Diseases, REVEALS, Exome Sequencing, Genetics, BREAST-CANCER, cancer, exome, neoantigens, Humans, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Polymorphism, MET INHIBITORS, Genetic association, Science & Technology, IDENTIFICATION, Sequence Analysis, RNA, Human Genome, Neurosciences, PROTEÔMICA, SOMATIC MUTATIONS, MASS-SPECTROMETRY, Cell Biology, neoantigen, 030104 developmental biology, biology.protein, RNA, Neoplasm, Human genome, 1109 Neurosciences
Abstract: Cancer Cell, 34 (2), ISSN:1535-6108, ISSN:1878-3686
Published: 2018

25. Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas

Author: Yang Liu, Nilay S. Sethi, Toshinori Hinoue, Barbara G. Schneider, Andrew D. Cherniack, Francisco Sanchez-Vega, Jose A. Seoane, Farshad Farshidfar, Reanne Bowlby, Mirazul Islam, Jaegil Kim, Walid Chatila, Rehan Akbani, Rupa S. Kanchi, Charles S. Rabkin, Joseph E. Willis, Kenneth K. Wang, Shannon J. McCall, Lopa Mishra, Akinyemi I. Ojesina, Susan Bullman, Chandra Sekhar Pedamallu, Alexander J. Lazar, Ryo Sakai, Vésteinn Thorsson, Adam J. Bass, Peter W. Laird, Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, Gad Getz, David I. Heiman, Michael S. Lawrence, Pei Lin, Sam Meier, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Yuexin Liu, Michael Miller, Sheila Reynolds, Ilya Shmulevich, Vesteinn Thorsson, Wei Zhang, Bradley M. Broom, Apurva M. Hegde, Zhenlin Ju, Anil Korkut, Jun Li, Han Liang, Shiyun Ling, Wenbin Liu, Yiling Lu, Gordon B. Mills, Kwok-Shing Ng, Arvind Rao, Michael Ryan, Jing Wang, John N. Weinstein, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K. Chatila, Inode Bruijn, Jianjiong Gao, Benjamin E. Gross, Zachary J. Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G. Nissan, Angelica Ochoa, Sarah M. Phillips, Ed Reznik, Chris Sander, Nikolaus Schultz, Robert Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, Joshua M. Stuart, Christopher K. Wong, Christina Yau, D. Neil Hayes, Joel S. Parker, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, A. Gordon Robertson, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Ashton C. Berger, Rameen Beroukhim, Carrie Cibulskis, Stacey B. Gabriel, Galen F. Gao, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju S. Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz S. Bootwalla, Phillip H. Lai, Dennis T. Maglinte, David J. Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Cheng Fan, Katherine A. Hoadley, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Amy H. Perou, Charles M. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Huihui Fan, Hui Shen, Wanding Zhou, Michelle Bellair, Kyle Chang, Kyle Covington, Chad J. Creighton, Huyen Dinh, HarshaVardhan Doddapaneni, Lawrence A. Donehower, Jennifer Drummond, Richard A. Gibbs, Robert Glenn, Walker Hale, Yi Han, Jianhong Hu, Viktoriya Korchina, Sandra Lee, Lora Lewis, Wei Li, Xiuping Liu, Margaret Morgan, Donna Morton, Donna Muzny, Jireh Santibanez, Margi Sheth, Eve Shinbrot, Linghua Wang, Min Wang, David A. Wheeler, Liu Xi, Fengmei Zhao, Julian Hess, Elizabeth L. Appelbaum, Matthew Bailey, Matthew G. Cordes, Li Ding, Catrina C. Fronick, Lucinda A. Fulton, Robert S. Fulton, Cyriac Kandoth, Elaine R. Mardis, Michael D. McLellan, Christopher A. Miller, Heather K. Schmidt, Richard K. Wilson, Daniel Crain, Erin Curley, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Mark Sherman, Eric Thompson, Peggy Yena, Jay Bowen, Julie M. Gastier-Foster, Mark Gerken, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Niall Corcoran, Tony Costello, Christopher Hovens, Andre L. Carvalho, Ana C. de Carvalho, José H. Fregnani, Adhemar Longatto-Filho, Rui M. Reis, Cristovam Scapulatempo-Neto, Henrique C.S. Silveira, Daniel O. Vidal, Andrew Burnette, Jennifer Eschbacher, Beth Hermes, Ardene Noss, Rosy Singh, Matthew L. Anderson, Patricia D. Castro, Michael Ittmann, David Huntsman, Bernard Kohl, Xuan Le, Richard Thorp, Chris Andry, Elizabeth R. Duffy, Vladimir Lyadov, Oxana Paklina, Galiya Setdikova, Alexey Shabunin, Mikhail Tavobilov, Christopher McPherson, Ronald Warnick, Ross Berkowitz, Daniel Cramer, Colleen Feltmate, Neil Horowitz, Adam Kibel, Michael Muto, Chandrajit P. Raut, Andrei Malykh, Jill S. Barnholtz-Sloan, Wendi Barrett, Karen Devine, Jordonna Fulop, Quinn T. Ostrom, Kristen Shimmel, Yingli Wolinsky, Andrew E. Sloan, Agostino De Rose, Felice Giuliante, Marc Goodman, Beth Y. Karlan, Curt H. Hagedorn, John Eckman, Jodi Harr, Jerome Myers, Kelinda Tucker, Leigh Anne Zach, Brenda Deyarmin, Hai Hu, Leonid Kvecher, Caroline Larson, Richard J. Mural, Stella Somiari, Ales Vicha, Tomas Zelinka, Joseph Bennett, Mary Iacocca, Brenda Rabeno, Patricia Swanson, Mathieu Latour, Louis Lacombe, Bernard Têtu, Alain Bergeron, Mary McGraw, Susan M. Staugaitis, John Chabot, Hanina Hibshoosh, Antonia Sepulveda, Tao Su, Timothy Wang, Olga Potapova, Olga Voronina, Laurence Desjardins, Odette Mariani, Sergio Roman-Roman, Xavier Sastre, Marc-Henri Stern, Feixiong Cheng, Sabina Signoretti, Andrew Berchuck, Darell Bigner, Eric Lipp, Jeffrey Marks, Shannon McCall, Roger McLendon, Angeles Secord, Alexis Sharp, Madhusmita Behera, Daniel J. Brat, Amy Chen, Keith Delman, Seth Force, Fadlo Khuri, Kelly Magliocca, Shishir Maithel, Jeffrey J. Olson, Taofeek Owonikoko, Alan Pickens, Suresh Ramalingam, Dong M. Shin, Gabriel Sica, Erwin G. Van Meir, Hongzheng Zhang, Wil Eijckenboom, Ad Gillis, Esther Korpershoek, Leendert Looijenga, Wolter Oosterhuis, Hans Stoop, Kim E. van Kessel, Ellen C. Zwarthoff, Chiara Calatozzolo, Lucia Cuppini, Stefania Cuzzubbo, Francesco DiMeco, Gaetano Finocchiaro, Luca Mattei, Alessandro Perin, Bianca Pollo, Chu Chen, John Houck, Pawadee Lohavanichbutr, Arndt Hartmann, Christine Stoehr, Robert Stoehr, Helge Taubert, Sven Wach, Bernd Wullich, Witold Kycler, Dawid Murawa, Maciej Wiznerowicz, Ki Chung, W. Jeffrey Edenfield, Julie Martin, Eric Baudin, Glenn Bubley, Raphael Bueno, Assunta De Rienzo, William G. 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C., Jungk C., Unterberg A., von Deimling A., Bossler A., Galbraith J., Jacobus L., Knudson M., Knutson T., Ma D., Milhem M., Sigmund R., Godwin A.K., Madan R., Rosenthal H.G., Adebamowo C., Adebamowo S.N., Boussioutas A., Beer D., Giordano T., Mes-Masson A.-M., Saad F., Bocklage T., Landrum L., Mannel R., Moore K., Moxley K., Postier R., Walker J., Zuna R., Feldman M., Valdivieso F., Dhir R., Luketich J., Pinero E.M.M., Quintero-Aguilo M., Carlotti C.G., Dos Santos J.S., Kemp R., Sankarankuty A., Tirapelli D., Catto J., Agnew K., Swisher E., Creaney J., Robinson B., Shelley C.S., Godwin E.M., Kendall S., Shipman C., Bradford C., Carey T., Haddad A., Moyer J., Peterson L., Prince M., Rozek L., Wolf G., Bowman R., Fong K.M., Yang I., Korst R., Rathmell W.K., Fantacone-Campbell J.L., Hooke J.A., Kovatich A.J., Shriver C.D., DiPersio J., Drake B., Govindan R., Heath S., Ley T., Van Tine B., Westervelt P., Rubin M.A., Lee J.I., Aredes N.D., Mariamidze A., and Bass A.J.
Subjects: 0301 basic medicine, Male, Cancer Research, Colorectal cancer, MICROSATELLITE INSTABILITY, Cancer Genome Atlas Research Network, medicine.disease_cause, Heterogeneous-Nuclear Ribonucleoproteins, COLORECTAL-CANCER, Epigenesis, Genetic, genomic, Chromosome instability, LS2_1, LS4_6, rectum, Gene Regulatory Networks, 610 Medicine & health, Poly-ADP-Ribose Binding Proteins, Poly-ADP-Ribose Binding Protein, Gastrointestinal Neoplasms, colorectal, Gene Regulatory Network, NEOPLASIAS GASTROINTESTINAIS, RNA-Binding Proteins, SOX9 Transcription Factor, DNA-Binding Proteins, GENOME, Oncology, Gastrointestinal Neoplasm, DNA methylation, Adenocarcinoma, Female, KRAS, NK CELLS, MutL Protein Homolog 1, Life Sciences & Biomedicine, STEM-CELLS, epigenetic, stomach, Human, tumor, esophagu, cancer, colon, esophagus, methylation, Biology, MLH1, Polymorphism, Single Nucleotide, Article, NO, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, Chromosomal Instability, medicine, Humans, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Science & Technology, CpG Island Methylator Phenotype, MUTATIONS, HUMAN-CELLS, Microsatellite instability, DNA, DNA Polymerase II, Cell Biology, DNA Methylation, medicine.disease, Aneuploidy, digestive system diseases, 030104 developmental biology, Mutation, Cancer research, Heterogeneous-Nuclear Ribonucleoprotein, GENERATION SEQUENCING DATA, 1109 Neurosciences, GASTRIC-CANCER
Abstract: We analyzed 921 adenocarcinomas of the esophagus, stomach, colon, and rectum to examine shared and distinguishing molecular characteristics of gastrointestinal tract adenocarcinomas (GIACs). Hypermutated tumors were distinct regardless of cancer type and comprised those enriched for insertions/deletions, representing microsatellite instability cases with epigenetic silencing of MLH1 in the context of CpG island methylator phenotype, plus tumors with elevated single-nucleotide variants associated with mutations in POLE. Tumors with chromosomal instability were diverse, with gastroesophageal adenocarcinomas harboring fragmented genomes associated with genomic doubling and distinct mutational signatures. We identified a group of tumors in the colon and rectum lacking hypermutation and aneuploidy termed genome stable and enriched in DNA hypermethylation and mutations in KRAS, SOX9, and PCBP1. Liu et al. analyze 921 gastrointestinal (GI) tract adenocarcinomas and find that hypermutated tumors are enriched for insertions/deletions, upper GI tumors with chromosomal instability harbor fragmented genomes, and a group of genome-stable colorectal tumors are enriched in mutations in SOX9 and PCBP1.
Published: 2018

26. Perspective on Oncogenic Processes at the End of the Beginning of Cancer Genomics

Author: Li Ding, Matthew H. Bailey, Eduard Porta-Pardo, Vesteinn Thorsson, Antonio Colaprico, Denis Bertrand, David L. Gibbs, Amila Weerasinghe, Kuan-lin Huang, Collin Tokheim, Isidro Cortés-Ciriano, Reyka Jayasinghe, Feng Chen, Lihua Yu, Sam Sun, Catharina Olsen, Jaegil Kim, Alison M. Taylor, Andrew D. Cherniack, Rehan Akbani, Chayaporn Suphavilai, Niranjan Nagarajan, Joshua M. Stuart, Gordon B. Mills, Matthew A. Wyczalkowski, Benjamin G. Vincent, Carolyn M. Hutter, Jean Claude Zenklusen, Katherine A. Hoadley, Michael C. Wendl, llya Shmulevich, Alexander J. Lazar, David A. Wheeler, Gad Getz, Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, David I. Heiman, Michael S. Lawrence, Pei Lin, Sam Meier, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Yuexin Liu, Michael Miller, Sheila Reynolds, Ilya Shmulevich, Wei Zhang, Bradley M. Broom, Apurva M. Hegde, Zhenlin Ju, Rupa S. Kanchi, Anil Korkut, Jun Li, Han Liang, Shiyun Ling, Wenbin Liu, Yiling Lu, Kwok-Shing Ng, Arvind Rao, Michael Ryan, Jing Wang, John N. Weinstein, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K. Chatila, Ino de Bruijn, Jianjiong Gao, Benjamin E. Gross, Zachary J. Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G. Nissan, Angelica Ochoa, Sarah M. Phillips, Ed Reznik, Francisco Sanchez-Vega, Chris Sander, Nikolaus Schultz, Robert Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, Christopher K. Wong, Christina Yau, D. Neil Hayes, Joel S. Parker, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, A. Gordon Robertson, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Ashton C. Berger, Rameen Beroukhim, Carrie Cibulskis, Stacey B. Gabriel, Galen F. Gao, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju S. Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz S. Bootwalla, Phillip H. Lai, Dennis T. Maglinte, David J. Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Cheng Fan, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Amy H. Perou, Charles M. Perou, Jeffrey Roach, Yan Shi, Janae V. 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Wilson, Daniel Crain, Erin Curley, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Mark Sherman, Eric Thompson, Peggy Yena, Jay Bowen, Julie M. Gastier-Foster, Mark Gerken, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Niall Corcoran, Tony Costello, Christopher Hovens, Andre L. Carvalho, Ana C. de Carvalho, José H. Fregnani, Adhemar Longatto-Filho, Rui M. Reis, Cristovam Scapulatempo-Neto, Henrique C.S. Silveira, Daniel O. Vidal, Andrew Burnette, Jennifer Eschbacher, Beth Hermes, Ardene Noss, Rosy Singh, Matthew L. Anderson, Patricia D. Castro, Michael Ittmann, David Huntsman, Bernard Kohl, Xuan Le, Richard Thorp, Chris Andry, Elizabeth R. Duffy, Vladimir Lyadov, Oxana Paklina, Galiya Setdikova, Alexey Shabunin, Mikhail Tavobilov, Christopher McPherson, Ronald Warnick, Ross Berkowitz, Daniel Cramer, Colleen Feltmate, Neil Horowitz, Adam Kibel, Michael Muto, Chandrajit P. Raut, Andrei Malykh, Jill S. Barnholtz-Sloan, Wendi Barrett, Karen Devine, Jordonna Fulop, Quinn T. Ostrom, Kristen Shimmel, Yingli Wolinsky, Andrew E. Sloan, Agostino De Rose, Felice Giuliante, Marc Goodman, Beth Y. Karlan, Curt H. Hagedorn, John Eckman, Jodi Harr, Jerome Myers, Kelinda Tucker, Leigh Anne Zach, Brenda Deyarmin, Hai Hu, Leonid Kvecher, Caroline Larson, Richard J. Mural, Stella Somiari, Ales Vicha, Tomas Zelinka, Joseph Bennett, Mary Iacocca, Brenda Rabeno, Patricia Swanson, Mathieu Latour, Louis Lacombe, Bernard Têtu, Alain Bergeron, Mary McGraw, Susan M. Staugaitis, John Chabot, Hanina Hibshoosh, Antonia Sepulveda, Tao Su, Timothy Wang, Olga Potapova, Olga Voronina, Laurence Desjardins, Odette Mariani, Sergio Roman-Roman, Xavier Sastre, Marc-Henri Stern, Feixiong Cheng, Sabina Signoretti, Andrew Berchuck, Darell Bigner, Eric Lipp, Jeffrey Marks, Shannon McCall, Roger McLendon, Angeles Secord, Alexis Sharp, Madhusmita Behera, Daniel J. Brat, Amy Chen, Keith Delman, Seth Force, Fadlo Khuri, Kelly Magliocca, Shishir Maithel, Jeffrey J. Olson, Taofeek Owonikoko, Alan Pickens, Suresh Ramalingam, Dong M. Shin, Gabriel Sica, Erwin G. Van Meir, Hongzheng Zhang, Wil Eijckenboom, Ad Gillis, Esther Korpershoek, Leendert Looijenga, Wolter Oosterhuis, Hans Stoop, Kim E. van Kessel, Ellen C. Zwarthoff, Chiara Calatozzolo, Lucia Cuppini, Stefania Cuzzubbo, Francesco DiMeco, Gaetano Finocchiaro, Luca Mattei, Alessandro Perin, Bianca Pollo, Chu Chen, John Houck, Pawadee Lohavanichbutr, Arndt Hartmann, Christine Stoehr, Robert Stoehr, Helge Taubert, Sven Wach, Bernd Wullich, Witold Kycler, Dawid Murawa, Maciej Wiznerowicz, Ki Chung, W. Jeffrey Edenfield, Julie Martin, Eric Baudin, Glenn Bubley, Raphael Bueno, Assunta De Rienzo, William G. Richards, Steven Kalkanis, Tom Mikkelsen, Houtan Noushmehr, Lisa Scarpace, Nicolas Girard, Marta Aymerich, Elias Campo, Eva Giné, Armando López Guillermo, Nguyen Van Bang, Phan Thi Hanh, Bui Duc Phu, Yufang Tang, Howard Colman, Kimberley Evason, Peter R. Dottino, John A. Martignetti, Hani Gabra, Hartmut Juhl, Teniola Akeredolu, Serghei Stepa, Dave Hoon, Keunsoo Ahn, Koo Jeong Kang, Felix Beuschlein, Anne Breggia, Michael Birrer, Debra Bell, Mitesh Borad, Alan H. Bryce, Erik Castle, Vishal Chandan, John Cheville, John A. Copland, Michael Farnell, Thomas Flotte, Nasra Giama, Thai Ho, Michael Kendrick, Jean-Pierre Kocher, Karla Kopp, Catherine Moser, David Nagorney, Daniel O’Brien, Brian Patrick O’Neill, Tushar Patel, Gloria Petersen, Florencia Que, Michael Rivera, Lewis Roberts, Robert Smallridge, Thomas Smyrk, Melissa Stanton, R. Houston Thompson, Michael Torbenson, Ju Dong Yang, Lizhi Zhang, Fadi Brimo, Jaffer A. Ajani, Ana Maria Angulo Gonzalez, Carmen Behrens, Jolanta Bondaruk, Russell Broaddus, Bogdan Czerniak, Bita Esmaeli, Junya Fujimoto, Jeffrey Gershenwald, Charles Guo, Christopher Logothetis, Funda Meric-Bernstam, Cesar Moran, Lois Ramondetta, David Rice, Anil Sood, Pheroze Tamboli, Timothy Thompson, Patricia Troncoso, Anne Tsao, Ignacio Wistuba, Candace Carter, Lauren Haydu, Peter Hersey, Valerie Jakrot, Hojabr Kakavand, Richard Kefford, Kenneth Lee, Georgina Long, Graham Mann, Michael Quinn, Robyn Saw, Richard Scolyer, Kerwin Shannon, Andrew Spillane, Jonathan Stretch, Maria Synott, John Thompson, James Wilmott, Hikmat Al-Ahmadie, Timothy A. Chan, Ronald Ghossein, Anuradha Gopalan, Douglas A. Levine, Victor Reuter, Samuel Singer, Bhuvanesh Singh, Nguyen Viet Tien, Thomas Broudy, Cyrus Mirsaidi, Praveen Nair, Paul Drwiega, Judy Miller, Jennifer Smith, Howard Zaren, Joong-Won Park, Nguyen Phi Hung, Electron Kebebew, W. Marston Linehan, Adam R. Metwalli, Karel Pacak, Peter A. 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Mora Pinero, Mario Quintero-Aguilo, Carlos Gilberto Carlotti, Jose Sebastião Dos Santos, Rafael Kemp, Ajith Sankarankuty, Daniela Tirapelli, James Catto, Kathy Agnew, Elizabeth Swisher, Jenette Creaney, Bruce Robinson, Carl Simon Shelley, Eryn M. Godwin, Sara Kendall, Cassaundra Shipman, Carol Bradford, Thomas Carey, Andrea Haddad, Jeffey Moyer, Lisa Peterson, Mark Prince, Laura Rozek, Gregory Wolf, Rayleen Bowman, Kwun M. Fong, Ian Yang, Robert Korst, W. Kimryn Rathmell, J. Leigh Fantacone-Campbell, Jeffrey A. Hooke, Albert J. Kovatich, Craig D. Shriver, John DiPersio, Bettina Drake, Ramaswamy Govindan, Sharon Heath, Timothy Ley, Brian Van Tine, Peter Westervelt, Mark A. Rubin, Jung Il Lee, Natália D. Aredes, Armaz Mariamidze, Ding L., Bailey M.H., Porta-Pardo E., Thorsson V., Colaprico A., Bertrand D., Gibbs D.L., Weerasinghe A., Huang K.-L., Tokheim C., Cortes-Ciriano I., Jayasinghe R., Chen F., Yu L., Sun S., Olsen C., Kim J., Taylor A.M., Cherniack A.D., Akbani R., Suphavilai C., Nagarajan N., Stuart J.M., Mills G.B., Wyczalkowski M.A., Vincent B.G., Hutter C.M., Zenklusen J.C., Hoadley K.A., Wendl M.C., Shmulevich L., Lazar A.J., Wheeler D.A., Getz G., Caesar-Johnson S.J., Demchok J.A., Felau I., Kasapi M., Ferguson M.L., Sofia H.J., Tarnuzzer R., Wang Z., Yang L., Zhang J.J., Chudamani S., Liu J., Lolla L., Naresh R., Pihl T., Sun Q., Wan Y., Wu Y., Cho J., DeFreitas T., Frazer S., Gehlenborg N., Heiman D.I., Lawrence M.S., Lin P., Meier S., Noble M.S., Saksena G., Voet D., Zhang H., Bernard B., Chambwe N., Dhankani V., Knijnenburg T., Kramer R., Leinonen K., Liu Y., Miller M., Reynolds S., Shmulevich I., Zhang W., Broom B.M., Hegde A.M., Ju Z., Kanchi R.S., Korkut A., Li J., 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Weisenberger D.J., Auman J.T., Balu S., Bodenheimer T., Fan C., Hoyle A.P., Jefferys S.R., Jones C.D., Meng S., Mieczkowski P.A., Mose L.E., Perou A.H., Perou C.M., Roach J., Shi Y., Simons J.V., Skelly T., Soloway M.G., Tan D., Veluvolu U., Fan H., Hinoue T., Laird P.W., Shen H., Zhou W., Bellair M., Chang K., Covington K., Creighton C.J., Dinh H., Doddapaneni H., Donehower L.A., Drummond J., Gibbs R.A., Glenn R., Hale W., Han Y., Hu J., Korchina V., Lee S., Lewis L., Li W., Liu X., Morgan M., Morton D., Muzny D., Santibanez J., Sheth M., Shinbrot E., Wang L., Wang M., Xi L., Zhao F., Hess J., Appelbaum E.L., Bailey M., Cordes M.G., Fronick C.C., Fulton L.A., Fulton R.S., Kandoth C., Mardis E.R., McLellan M.D., Miller C.A., Schmidt H.K., Wilson R.K., Crain D., Curley E., Gardner J., Lau K., Mallery D., Morris S., Paulauskis J., Penny R., Shelton C., Shelton T., Sherman M., Thompson E., Yena P., Bowen J., Gastier-Foster J.M., Gerken M., Leraas K.M., Lichtenberg T.M., Ramirez N.C., Wise 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sciences, Medical Genetics, Medical Sociology, SAIC-F-Frederick, Inc, and Leidos Biomedical Research, Inc.
Subjects: 0301 basic medicine, oncogenic process, INFORMATION, DNA Repair, Tumor Microenvironment/genetics, Carcinogenesis, Cancer Genome Atlas Research Network, medicine.disease_cause, Genome, Biochemistry, Germline, Transcriptome, oncogenic proce, Neoplasms, Databases, Genetic, LS2_1, Tumor Microenvironment, LS4_6, SOMATIC POINT MUTATIONS, 610 Medicine & health, 11 Medical and Health Sciences, Carcinogenesi, Metabolic Networks and Pathways/genetics, cancer genomic, CARCINOGÊNESE, Genomics, TUMORS, Neoplasms/genetics, omics, Proteome, Physique des particules élémentaires, Microsatellite Instability, Life Sciences & Biomedicine, Metabolic Networks and Pathways, Human, EXPRESSION, Biochemistry & Molecular Biology, cancer, cancer genomics, TCGA, omic, Computational biology, Biology, BREAST, CLASSIFICATION, General Biochemistry, Genetics and Molecular Biology, Article, NO, 03 medical and health sciences, DNA Repair/genetics, medicine, Humans, Tumor microenvironment, Science & Technology, LANDSCAPE, IDENTIFICATION, Biochemistry, Genetics and Molecular Biology(all), Metabolic Networks and Pathway, Cell Biology, Epigenome, 06 Biological Sciences, 030104 developmental biology, DISCOVERY, Mutation, DRIVER, Neoplasm, Carcinogenesis/genetics, Developmental Biology, Genetics and Molecular Biology(all), Genes, Neoplasm
Abstract: The Cancer Genome Atlas (TCGA) has catalyzed systematic characterization of diverse genomic alterations underlying human cancers. At this historic junction marking the completion of genomic characterization of over 11,000 tumors from 33 cancer types, we present our current understanding of the molecular processes governing oncogenesis. We illustrate our insights into cancer through synthesis of the findings of the TCGA PanCancer Atlas project on three facets of oncogenesis: (1) somatic driver mutations, germline pathogenic variants, and their interactions in the tumor; (2) the influence of the tumor genome and epigenome on transcriptome and proteome; and (3) the relationship between tumor and the microenvironment, including implications for drugs targeting driver events and immunotherapies. These results will anchor future characterization of rare and common tumor types, primary and relapsed tumors, and cancers across ancestry groups and will guide the deployment of clinical genomic sequencing. A synthesized view on oncogenic processes based on PanCancer Atlas analyses highlights the complex impact of genome alterations on the signaling and multi-omic profiles of human cancers as well as their influence on tumor microenvironment., 0, info:eu-repo/semantics/published
Published: 2018

27. An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

Author: Jianfang Liu, Tara Lichtenberg, Katherine A. Hoadley, Laila M. Poisson, Alexander J. Lazar, Andrew D. Cherniack, Albert J. Kovatich, Christopher C. Benz, Douglas A. Levine, Adrian V. Lee, Larsson Omberg, Denise M. Wolf, Craig D. Shriver, Vesteinn Thorsson, Hai Hu, Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, Gad Getz, David I. Heiman, Jaegil Kim, Michael S. Lawrence, Pei Lin, Sam Meier, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Yuexin Liu, Michael Miller, Sheila Reynolds, Ilya Shmulevich, Wei Zhang, Rehan Akbani, Bradley M. Broom, Apurva M. Hegde, Zhenlin Ju, Rupa S. Kanchi, Anil Korkut, Jun Li, Han Liang, Shiyun Ling, Wenbin Liu, Yiling Lu, Gordon B. Mills, Kwok-Shing Ng, Arvind Rao, Michael Ryan, Jing Wang, John N. Weinstein, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K. Chatila, Ino de Bruijn, Jianjiong Gao, Benjamin E. Gross, Zachary J. Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G. Nissan, Angelica Ochoa, Sarah M. Phillips, Ed Reznik, Francisco Sanchez-Vega, Chris Sander, Nikolaus Schultz, Robert Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, Joshua M. Stuart, Christopher K. Wong, Christina Yau, D. Neil Hayes, Joel S. Parker, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, A. Gordon Robertson, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Ashton C. Berger, Rameen Beroukhim, Carrie Cibulskis, Stacey B. Gabriel, Galen F. Gao, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju S. Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz S. Bootwalla, Phillip H. Lai, Dennis T. Maglinte, David J. Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Cheng Fan, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Amy H. Perou, Charles M. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Huihui Fan, Toshinori Hinoue, Peter W. Laird, Hui Shen, Wanding Zhou, Michelle Bellair, Kyle Chang, Kyle Covington, Chad J. Creighton, Huyen Dinh, HarshaVardhan Doddapaneni, Lawrence A. Donehower, Jennifer Drummond, Richard A. Gibbs, Robert Glenn, Walker Hale, Yi Han, Jianhong Hu, Viktoriya Korchina, Sandra Lee, Lora Lewis, Wei Li, Xiuping Liu, Margaret Morgan, Donna Morton, Donna Muzny, Jireh Santibanez, Margi Sheth, Eve Shinbro, Linghua Wang, Min Wang, David A. Wheeler, Liu Xi, Fengmei Zhao, Julian Hess, Elizabeth L. Appelbaum, Matthew Bailey, Matthew G. Cordes, Li Ding, Catrina C. Fronick, Lucinda A. Fulton, Robert S. Fulton, Cyriac Kandoth, Elaine R. Mardis, Michael D. McLellan, Christopher A. Miller, Heather K. Schmidt, Richard K. Wilson, Daniel Crain, Erin Curley, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Mark Sherman, Eric Thompson, Peggy Yena, Jay Bowen, Julie M. Gastier-Foster, Mark Gerken, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Niall Corcoran, Tony Costello, Christopher Hovens, Andre L. Carvalho, Ana C. de Carvalho, José H. Fregnani, Adhemar Longatto-Filho, Rui M. Reis, Cristovam Scapulatempo-Neto, Henrique C.S. Silveira, Daniel O. Vidal, Andrew Burnette, Jennifer Eschbacher, Beth Hermes, Ardene Noss, Rosy Singh, Matthew L. Anderson, Patricia D. Castro, Michael Ittmann, David Huntsman, Bernard Kohl, Xuan Le, Richard Thorp, Chris Andry, Elizabeth R. Duffy, Vladimir Lyadov, Oxana Paklina, Galiya Setdikova, Alexey Shabunin, Mikhail Tavobilov, Christopher McPherson, Ronald Warnick, Ross Berkowitz, Daniel Cramer, Colleen Feltmate, Neil Horowitz, Adam Kibel, Michael Muto, Chandrajit P. Raut, Andrei Malykh, Jill S. Barnholtz-Sloan, Wendi Barrett, Karen Devine, Jordonna Fulop, Quinn T. Ostrom, Kristen Shimmel, Yingli Wolinsky, Andrew E. Sloan, Agostino De Rose, Felice Giuliante, Marc Goodman, Beth Y. Karlan, Curt H. Hagedorn, John Eckman, Jodi Harr, Jerome Myers, Kelinda Tucker, Leigh Anne Zach, Brenda Deyarmin, Leonid Kvecher, Caroline Larson, Richard J. Mural, Stella Somiari, Ales Vicha, Tomas Zelinka, Joseph Bennett, Mary Iacocca, Brenda Rabeno, Patricia Swanson, Mathieu Latour, Louis Lacombe, Bernard Têtu, Alain Bergeron, Mary McGraw, Susan M. Staugaitis, John Chabot, Hanina Hibshoosh, Antonia Sepulveda, Tao Su, Timothy Wang, Olga Potapova, Olga Voronina, Laurence Desjardins, Odette Mariani, Sergio Roman-Roman, Xavier Sastre, Marc-Henri Stern, Feixiong Cheng, Sabina Signoretti, Andrew Berchuck, Darell Bigner, Eric Lipp, Jeffrey Marks, Shannon McCall, Roger McLendon, Angeles Secord, Alexis Sharp, Madhusmita Behera, Daniel J. Brat, Amy Chen, Keith Delman, Seth Force, Fadlo Khuri, Kelly Magliocca, Shishir Maithel, Jeffrey J. Olson, Taofeek Owonikoko, Alan Pickens, Suresh Ramalingam, Dong M. Shin, Gabriel Sica, Erwin G. Van Meir, Hongzheng Zhang, Wil Eijckenboom, Ad Gillis, Esther Korpershoek, Leendert Looijenga, Wolter Oosterhuis, Hans Stoop, Kim E. van Kessel, Ellen C. Zwarthoff, Chiara Calatozzolo, Lucia Cuppini, Stefania Cuzzubbo, Francesco DiMeco, Gaetano Finocchiaro, Luca Mattei, Alessandro Perin, Bianca Pollo, Chu Chen, John Houck, Pawadee Lohavanichbutr, Arndt Hartmann, Christine Stoehr, Robert Stoehr, Helge Taubert, Sven Wach, Bernd Wullich, Witold Kycler, Dawid Murawa, Maciej Wiznerowicz, Ki Chung, W. Jeffrey Edenfield, Julie Martin, Eric Baudin, Glenn Bubley, Raphael Bueno, Assunta De Rienzo, William G. Richards, Steven Kalkanis, Tom Mikkelsen, Houtan Noushmehr, Lisa Scarpace, Nicolas Girard, Marta Aymerich, Elias Campo, Eva Giné, Armando López Guillermo, Nguyen Van Bang, Phan Thi Hanh, Bui Duc Phu, Yufang Tang, Howard Colman, Kimberley Evason, Peter R. Dottino, John A. Martignetti, Hani Gabra, Hartmut Juhl, Teniola Akeredolu, Serghei Stepa, Dave Hoon, Keunsoo Ahn, Koo Jeong Kang, Felix Beuschlein, Anne Breggia, Michael Birrer, Debra Bell, Mitesh Borad, Alan H. Bryce, Erik Castle, Vishal Chandan, John Cheville, John A. Copland, Michael Farnell, Thomas Flotte, Nasra Giama, Thai Ho, Michael Kendrick, Jean-Pierre Kocher, Karla Kopp, Catherine Moser, David Nagorney, Daniel O’Brien, Brian Patrick O’Neill, Tushar Patel, Gloria Petersen, Florencia Que, Michael Rivera, Lewis Roberts, Robert Smallridge, Thomas Smyrk, Melissa Stanton, R. Houston Thompson, Michael Torbenson, Ju Dong Yang, Lizhi Zhang, Fadi Brimo, Jaffer A. Ajani, Ana Maria Angulo Gonzalez, Carmen Behrens, Jolanta Bondaruk, Russell Broaddus, Bogdan Czerniak, Bita Esmaeli, Junya Fujimoto, Jeffrey Gershenwald, Charles Guo, Christopher Logothetis, Funda Meric-Bernstam, Cesar Moran, Lois Ramondetta, David Rice, Anil Sood, Pheroze Tamboli, Timothy Thompson, Patricia Troncoso, Anne Tsao, Ignacio Wistuba, Candace Carter, Lauren Haydu, Peter Hersey, Valerie Jakrot, Hojabr Kakavand, Richard Kefford, Kenneth Lee, Georgina Long, Graham Mann, Michael Quinn, Robyn Saw, Richard Scolyer, Kerwin Shannon, Andrew Spillane, Jonathan Stretch, Maria Synott, John Thompson, James Wilmott, Hikmat Al-Ahmadie, Timothy A. Chan, Ronald Ghossein, Anuradha Gopalan, Victor Reuter, Samuel Singer, Bhuvanesh Singh, Nguyen Viet Tien, Thomas Broudy, Cyrus Mirsaidi, Praveen Nair, Paul Drwiega, Judy Miller, Jennifer Smith, Howard Zaren, Joong-Won Park, Nguyen Phi Hung, Electron Kebebew, W. Marston Linehan, Adam R. Metwalli, Karel Pacak, Peter A. Pinto, Mark Schiffman, Laura S. Schmidt, Cathy D. Vocke, Nicolas Wentzensen, Robert Worrell, Hannah Yang, Marc Moncrieff, Chandra Goparaju, Jonathan Melamed, Harvey Pass, Natalia Botnariuc, Irina Caraman, Mircea Cernat, Inga Chemencedji, Adrian Clipca, Serghei Doruc, Ghenadie Gorincioi, Sergiu Mura, Maria Pirtac, Irina Stancul, Diana Tcaciuc, Monique Albert, Iakovina Alexopoulou, Angel Arnaout, John Bartlett, Jay Engel, Sebastien Gilbert, Jeremy Parfitt, Harman Sekhon, George Thomas, Doris M. Rassl, Robert C. Rintoul, Carlo Bifulco, Raina Tamakawa, Walter Urba, Nicholas Hayward, Henri Timmers, Anna Antenucci, Francesco Facciolo, Gianluca Grazi, Mirella Marino, Roberta Merola, Ronald de Krijger, Anne-Paule Gimenez-Roqueplo, Alain Piché, Simone Chevalier, Ginette McKercher, Kivanc Birsoy, Gene Barnett, Cathy Brewer, Carol Farver, Theresa Naska, Nathan A. Pennell, Daniel Raymond, Cathy Schilero, Kathy Smolenski, Felicia Williams, Carl Morrison, Jeffrey A. Borgia, Michael J. Liptay, Mark Pool, Christopher W. Seder, Kerstin Junker, Mikhail Dinkin, George Manikhas, Domenico Alvaro, Maria Consiglia Bragazzi, Vincenzo Cardinale, Guido Carpino, Eugenio Gaudio, David Chesla, Sandra Cottingham, Michael Dubina, Fedor Moiseenko, Renumathy Dhanasekaran, Karl-Friedrich Becker, Klaus-Peter Janssen, Julia Slotta-Huspenina, Mohamed H. Abdel-Rahman, Dina Aziz, Sue Bell, Colleen M. Cebulla, Amy Davis, Rebecca Duell, J. Bradley Elder, Joe Hilty, Bahavna Kumar, James Lang, Norman L. Lehman, Randy Mandt, Phuong Nguyen, Robert Pilarski, Karan Rai, Lynn Schoenfield, Kelly Senecal, Paul Wakely, Paul Hansen, Ronald Lechan, James Powers, Arthur Tischler, William E. Grizzle, Katherine C. Sexton, Alison Kastl, Joel Henderson, Sima Porten, Jens Waldmann, Martin Fassnacht, Sylvia L. Asa, Dirk Schadendorf, Marta Couce, Markus Graefen, Hartwig Huland, Guido Sauter, Thorsten Schlomm, Ronald Simon, Pierre Tennstedt, Oluwole Olabode, Mark Nelson, Oliver Bathe, Peter R. Carroll, June M. Chan, Philip Disaia, Pat Glenn, Robin K. Kelley, Charles N. Landen, Joanna Phillips, Michael Prados, Jeffry Simko, Karen Smith-McCune, Scott VandenBerg, Kevin Roggin, Ashley Fehrenbach, Ady Kendler, Suzanne Sifri, Ruth Steele, Antonio Jimeno, Francis Carey, Ian Forgie, Massimo Mannelli, Michael Carney, Brenda Hernandez, Benito Campos, Christel Herold-Mende, Christin Jungk, Andreas Unterberg, Andreas von Deimling, Aaron Bossler, Joseph Galbraith, Laura Jacobus, Michael Knudson, Tina Knutson, Deqin Ma, Mohammed Milhem, Rita Sigmund, Andrew K. Godwin, Rashna Madan, Howard G. Rosenthal, Clement Adebamowo, Sally N. Adebamowo, Alex Boussioutas, David Beer, Thomas Giordano, Anne-Marie Mes-Masson, Fred Saad, Therese Bocklage, Lisa Landrum, Robert Mannel, Kathleen Moore, Katherine Moxley, Russel Postier, Joan Walker, Rosemary Zuna, Michael Feldman, Federico Valdivieso, Rajiv Dhir, James Luketich, Edna M. Mora Pinero, Mario Quintero-Aguilo, Carlos Gilberto Carlotti, Jr, Jose Sebastião Dos Santos, Rafael Kemp, Ajith Sankarankuty, Daniela Tirapelli, James Catto, Kathy Agnew, Elizabeth Swisher, Jenette Creaney, Bruce Robinson, Carl Simon Shelley, Eryn M. Godwin, Sara Kendall, Cassaundra Shipman, Carol Bradford, Thomas Carey, Andrea Haddad, Jeffey Moyer, Lisa Peterson, Mark Prince, Laura Rozek, Gregory Wolf, Rayleen Bowman, Kwun M. Fong, Ian Yang, Robert Korst, W. Kimryn Rathmell, J. Leigh Fantacone-Campbell, Jeffrey A. Hooke, John DiPersio, Bettina Drake, Ramaswamy Govindan, Sharon Heath, Timothy Ley, Brian Van Tine, Peter Westervelt, Mark A. Rubin, Jung Il Lee, Natália D. Aredes, Armaz Mariamidze, Liu J., Lichtenberg T., Hoadley K.A., Poisson L.M., Lazar A.J., Cherniack A.D., Kovatich A.J., Benz C.C., Levine D.A., Lee A.V., Omberg L., Wolf D.M., Shriver C.D., Thorsson V., Caesar-Johnson S.J., Demchok J.A., Felau I., Kasapi M., Ferguson M.L., Hutter C.M., Sofia H.J., Tarnuzzer R., Wang Z., Yang L., Zenklusen J.C., Zhang J.J., Chudamani S., Lolla L., Naresh R., Pihl T., Sun Q., Wan Y., Wu Y., Cho J., DeFreitas T., Frazer S., Gehlenborg N., Getz G., Heiman D.I., Kim J., Lawrence M.S., Lin P., Meier S., Noble M.S., Saksena G., Voet D., Zhang H., Bernard B., Chambwe N., Dhankani V., Knijnenburg T., Kramer R., Leinonen K., Liu Y., Miller M., Reynolds S., Shmulevich I., Zhang W., Akbani R., Broom B.M., Hegde A.M., Ju Z., Kanchi R.S., Korkut A., Li J., Liang H., Ling S., Liu W., Lu Y., Mills G.B., Ng K.-S., Rao A., Ryan M., Wang J., Weinstein J.N., Zhang J., Abeshouse A., Armenia J., Chakravarty D., Chatila W.K., de Bruijn I., Gao J., Gross B.E., Heins Z.J., Kundra R., La K., Ladanyi M., Luna A., Nissan M.G., Ochoa A., Phillips S.M., Reznik E., Sanchez-Vega F., Sander C., Schultz N., Sheridan R., Sumer S.O., Sun Y., Taylor B.S., Anur P., Peto M., Spellman P., Benz C., Stuart J.M., Wong C.K., Yau C., Hayes D.N., Parker J.S., Wilkerson M.D., Ally A., Balasundaram M., Bowlby R., Brooks D., Carlsen R., Chuah E., Dhalla N., Holt R., Jones S.J.M., Kasaian K., Lee D., Ma Y., Marra M.A., Mayo M., Moore R.A., Mungall A.J., Mungall K., Robertson A.G., Sadeghi S., Schein J.E., Sipahimalani P., Tam A., Thiessen N., Tse K., Wong T., Berger A.C., Beroukhim R., Cibulskis C., Gabriel S.B., Gao G.F., Ha G., Meyerson M., Schumacher S.E., Shih J., Kucherlapati M.H., Kucherlapati R.S., Baylin S., Cope L., Danilova L., Bootwalla M.S., Lai P.H., Maglinte D.T., Van Den Berg D.J., Weisenberger D.J., Auman J.T., Balu S., Bodenheimer T., Fan C., Hoyle A.P., Jefferys S.R., Jones C.D., Meng S., Mieczkowski P.A., Mose L.E., Perou A.H., Perou C.M., Roach J., Shi Y., Simons J.V., Skelly T., Soloway M.G., Tan D., Veluvolu U., Fan H., Hinoue T., Laird P.W., Shen H., Zhou W., Bellair M., Chang K., Covington K., Creighton C.J., Dinh H., Doddapaneni H., Donehower L.A., Drummond J., Gibbs R.A., Glenn R., Hale W., Han Y., Hu J., Korchina V., Lee S., Lewis L., Li W., Liu X., Morgan M., Morton D., Muzny D., Santibanez J., Sheth M., Shinbro E., Wang L., Wang M., Wheeler D.A., Xi L., Zhao F., Hess J., Appelbaum E.L., Bailey M., Cordes M.G., Ding L., Fronick C.C., Fulton L.A., Fulton R.S., Kandoth C., Mardis E.R., McLellan M.D., Miller C.A., Schmidt H.K., Wilson R.K., Crain D., Curley E., Gardner J., Lau K., Mallery D., Morris S., Paulauskis J., Penny R., Shelton C., Shelton T., Sherman M., Thompson E., Yena P., Bowen J., Gastier-Foster J.M., Gerken M., Leraas K.M., Lichtenberg T.M., Ramirez N.C., Wise L., Zmuda E., Corcoran N., Costello T., Hovens C., Carvalho A.L., de Carvalho A.C., Fregnani J.H., Longatto-Filho A., Reis R.M., Scapulatempo-Neto C., Silveira H.C.S., Vidal D.O., Burnette A., Eschbacher J., Hermes B., Noss A., Singh R., Anderson M.L., Castro P.D., Ittmann M., Huntsman D., Kohl B., Le X., Thorp R., Andry C., Duffy E.R., Lyadov V., Paklina O., Setdikova G., Shabunin A., Tavobilov M., McPherson C., Warnick R., Berkowitz R., Cramer D., Feltmate C., Horowitz N., Kibel A., Muto M., Raut C.P., Malykh A., Barnholtz-Sloan J.S., Barrett W., Devine K., Fulop J., Ostrom Q.T., Shimmel K., Wolinsky Y., Sloan A.E., De Rose A., Giuliante F., Goodman M., Karlan B.Y., Hagedorn C.H., Eckman J., Harr J., Myers J., Tucker K., Zach L.A., Deyarmin B., Hu H., Kvecher L., Larson C., Mural R.J., Somiari S., Vicha A., Zelinka T., Bennett J., Iacocca M., Rabeno B., Swanson P., Latour M., Lacombe L., Tetu B., Bergeron A., McGraw M., Staugaitis S.M., Chabot J., Hibshoosh H., Sepulveda A., Su T., Wang T., Potapova O., Voronina O., Desjardins L., Mariani O., Roman-Roman S., Sastre X., Stern M.-H., Cheng F., Signoretti S., Berchuck A., Bigner D., Lipp E., 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Subjects: 0301 basic medicine, Genetics and Molecular Biology (all), Cancer Genome Atlas Research Network, Kaplan-Meier Estimate, Biochemistry, DEFINITIONS, Neoplasms, Databases, Genetic, SUFFICIENT FOLLOW-UP, LS2_1, LS4_6, 11 Medical and Health Sciences, COMPREHENSIVE GENOMIC CHARACTERIZATION, Cox proportional hazards regression model, TAXA DE SOBREVIVÊNCIA, follow-up time, Genomics, 3. Good health, TIME, Life Sciences & Biomedicine, PROGRESSION-FREE SURVIVAL, Human, Biochemistry & Molecular Biology, overall survival, The Cancer Genome Atlas, Translational research, Computational biology, Biology, clinical data resource, disease-free interval, disease-specific survival, progression-free interval, TCGA, translational research, Article, General Biochemistry, Genetics and Molecular Biology, CLASSIFICATION, NO, 03 medical and health sciences, Annotation, Breast cancer, END-POINTS, medicine, BREAST-CANCER, Humans, Progression-free survival, RECURRENCE, Biochemistry, Genetics and Molecular Biology (all), Proportional Hazards Models, Data collection, Science & Technology, business.industry, MOLECULAR PORTRAITS, Biochemistry, Genetics and Molecular Biology(all), Cancer, Cell Biology, 06 Biological Sciences, medicine.disease, 030104 developmental biology, Analytics, Genomic, Neoplasm, business, The Cancer Genome Atla, Genetics and Molecular Biology(all), Developmental Biology
Abstract: SUMMARY For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale., Graphical abstract In Brief Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types.
Published: 2018

28. The Immune Landscape of Cancer

Author: Vésteinn Thorsson, David L. Gibbs, Scott D. Brown, Denise Wolf, Dante S. Bortone, Tai-Hsien Ou Yang, Eduard Porta-Pardo, Galen F. Gao, Christopher L. Plaisier, James A. Eddy, Elad Ziv, Aedin C. Culhane, Evan O. Paull, I.K. Ashok Sivakumar, Andrew J. Gentles, Raunaq Malhotra, Farshad Farshidfar, Antonio Colaprico, Joel S. Parker, Lisle E. Mose, Nam Sy Vo, Jianfang Liu, Yuexin Liu, Janet Rader, Varsha Dhankani, Sheila M. Reynolds, Reanne Bowlby, Andrea Califano, Andrew D. Cherniack, Dimitris Anastassiou, Davide Bedognetti, Younes Mokrab, Aaron M. Newman, Arvind Rao, Ken Chen, Alexander Krasnitz, Hai Hu, Tathiane M. Malta, Houtan Noushmehr, Chandra Sekhar Pedamallu, Susan Bullman, Akinyemi I. Ojesina, Andrew Lamb, Wanding Zhou, Hui Shen, Toni K. Choueiri, John N. Weinstein, Justin Guinney, Joel Saltz, Robert A. Holt, Charles S. Rabkin, Alexander J. Lazar, Jonathan S. Serody, Elizabeth G. Demicco, Mary L. Disis, Benjamin G. Vincent, Ilya Shmulevich, Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, Gad Getz, David I. Heiman, Jaegil Kim, Michael S. Lawrence, Pei Lin, Sam Meier, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Michael Miller, Sheila Reynolds, Vesteinn Thorsson, Wei Zhang, Rehan Akbani, Bradley M. Broom, Apurva M. Hegde, Zhenlin Ju, Rupa S. Kanchi, Anil Korkut, Jun Li, Han Liang, Shiyun Ling, Wenbin Liu, Yiling Lu, Gordon B. Mills, Kwok-Shing Ng, Michael Ryan, Jing Wang, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K. Chatila, Ino de Bruijn, Jianjiong Gao, Benjamin E. Gross, Zachary J. Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G. Nissan, Angelica Ochoa, Sarah M. Phillips, Ed Reznik, Francisco Sanchez-Vega, Chris Sander, Nikolaus Schultz, Robert Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, Joshua M. Stuart, Christopher K. Wong, Christina Yau, D. Neil Hayes, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, A. Gordon Robertson, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Ashton C. Berger, Rameen Beroukhim, Carrie Cibulskis, Stacey B. Gabriel, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju S. Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz S. Bootwalla, Phillip H. Lai, Dennis T. Maglinte, David J. Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Cheng Fan, Katherine A. Hoadley, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Amy H. Perou, Charles M. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Huihui Fan, Toshinori Hinoue, Peter W. Laird, Michelle Bellair, Kyle Chang, Kyle Covington, Chad J. Creighton, Huyen Dinh, HarshaVardhan Doddapaneni, Lawrence A. Donehower, Jennifer Drummond, Richard A. Gibbs, Robert Glenn, Walker Hale, Yi Han, Jianhong Hu, Viktoriya Korchina, Sandra Lee, Lora Lewis, Wei Li, Xiuping Liu, Margaret Morgan, Donna Morton, Donna Muzny, Jireh Santibanez, Margi Sheth, Eve Shinbrot, Linghua Wang, Min Wang, David A. Wheeler, Liu Xi, Fengmei Zhao, Julian Hess, Elizabeth L. Appelbaum, Matthew Bailey, Matthew G. Cordes, Li Ding, Catrina C. Fronick, Lucinda A. Fulton, Robert S. Fulton, Cyriac Kandoth, Elaine R. Mardis, Michael D. McLellan, Christopher A. Miller, Heather K. Schmidt, Richard K. Wilson, Daniel Crain, Erin Curley, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Mark Sherman, Eric Thompson, Peggy Yena, Jay Bowen, Julie M. Gastier-Foster, Mark Gerken, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Niall Corcoran, Tony Costello, Christopher Hovens, Andre L. Carvalho, Ana C. de Carvalho, José H. Fregnani, Adhemar Longatto-Filho, Rui M. Reis, Cristovam Scapulatempo-Neto, Henrique C.S. Silveira, Daniel O. Vidal, Andrew Burnette, Jennifer Eschbacher, Beth Hermes, Ardene Noss, Rosy Singh, Matthew L. Anderson, Patricia D. Castro, Michael Ittmann, David Huntsman, Bernard Kohl, Xuan Le, Richard Thorp, Chris Andry, Elizabeth R. Duffy, Vladimir Lyadov, Oxana Paklina, Galiya Setdikova, Alexey Shabunin, Mikhail Tavobilov, Christopher McPherson, Ronald Warnick, Ross Berkowitz, Daniel Cramer, Colleen Feltmate, Neil Horowitz, Adam Kibel, Michael Muto, Chandrajit P. Raut, Andrei Malykh, Jill S. Barnholtz-Sloan, Wendi Barrett, Karen Devine, Jordonna Fulop, Quinn T. Ostrom, Kristen Shimmel, Yingli Wolinsky, Andrew E. Sloan, Agostino De Rose, Felice Giuliante, Marc Goodman, Beth Y. Karlan, Curt H. Hagedorn, John Eckman, Jodi Harr, Jerome Myers, Kelinda Tucker, Leigh Anne Zach, Brenda Deyarmin, Leonid Kvecher, Caroline Larson, Richard J. Mural, Stella Somiari, Ales Vicha, Tomas Zelinka, Joseph Bennett, Mary Iacocca, Brenda Rabeno, Patricia Swanson, Mathieu Latour, Louis Lacombe, Bernard Têtu, Alain Bergeron, Mary McGraw, Susan M. Staugaitis, John Chabot, Hanina Hibshoosh, Antonia Sepulveda, Tao Su, Timothy Wang, Olga Potapova, Olga Voronina, Laurence Desjardins, Odette Mariani, Sergio Roman-Roman, Xavier Sastre, Marc-Henri Stern, Feixiong Cheng, Sabina Signoretti, Andrew Berchuck, Darell Bigner, Eric Lipp, Jeffrey Marks, Shannon McCall, Roger McLendon, Angeles Secord, Alexis Sharp, Madhusmita Behera, Daniel J. Brat, Amy Chen, Keith Delman, Seth Force, Fadlo Khuri, Kelly Magliocca, Shishir Maithel, Jeffrey J. Olson, Taofeek Owonikoko, Alan Pickens, Suresh Ramalingam, Dong M. Shin, Gabriel Sica, Erwin G. Van Meir, Hongzheng Zhang, Wil Eijckenboom, Ad Gillis, Esther Korpershoek, Leendert Looijenga, Wolter Oosterhuis, Hans Stoop, Kim E. van Kessel, Ellen C. Zwarthoff, Chiara Calatozzolo, Lucia Cuppini, Stefania Cuzzubbo, Francesco DiMeco, Gaetano Finocchiaro, Luca Mattei, Alessandro Perin, Bianca Pollo, Chu Chen, John Houck, Pawadee Lohavanichbutr, Arndt Hartmann, Christine Stoehr, Robert Stoehr, Helge Taubert, Sven Wach, Bernd Wullich, Witold Kycler, Dawid Murawa, Maciej Wiznerowicz, Ki Chung, W. Jeffrey Edenfield, Julie Martin, Eric Baudin, Glenn Bubley, Raphael Bueno, Assunta De Rienzo, William G. Richards, Steven Kalkanis, Tom Mikkelsen, Lisa Scarpace, Nicolas Girard, Marta Aymerich, Elias Campo, Eva Giné, Armando López Guillermo, Nguyen Van Bang, Phan Thi Hanh, Bui Duc Phu, Yufang Tang, Howard Colman, Kimberley Evason, Peter R. Dottino, John A. Martignetti, Hani Gabra, Hartmut Juhl, Teniola Akeredolu, Serghei Stepa, Dave Hoon, Keunsoo Ahn, Koo Jeong Kang, Felix Beuschlein, Anne Breggia, Michael Birrer, Debra Bell, Mitesh Borad, Alan H. Bryce, Erik Castle, Vishal Chandan, John Cheville, John A. Copland, Michael Farnell, Thomas Flotte, Nasra Giama, Thai Ho, Michael Kendrick, Jean-Pierre Kocher, Karla Kopp, Catherine Moser, David Nagorney, Daniel O’Brien, Brian Patrick O’Neill, Tushar Patel, Gloria Petersen, Florencia Que, Michael Rivera, Lewis Roberts, Robert Smallridge, Thomas Smyrk, Melissa Stanton, R. Houston Thompson, Michael Torbenson, Ju Dong Yang, Lizhi Zhang, Fadi Brimo, Jaffer A. Ajani, Ana Maria Angulo Gonzalez, Carmen Behrens, Jolanta Bondaruk, Russell Broaddus, Bogdan Czerniak, Bita Esmaeli, Junya Fujimoto, Jeffrey Gershenwald, Charles Guo, Christopher Logothetis, Funda Meric-Bernstam, Cesar Moran, Lois Ramondetta, David Rice, Anil Sood, Pheroze Tamboli, Timothy Thompson, Patricia Troncoso, Anne Tsao, Ignacio Wistuba, Candace Carter, Lauren Haydu, Peter Hersey, Valerie Jakrot, Hojabr Kakavand, Richard Kefford, Kenneth Lee, Georgina Long, Graham Mann, Michael Quinn, Robyn Saw, Richard Scolyer, Kerwin Shannon, Andrew Spillane, onathan Stretch, Maria Synott, John Thompson, James Wilmott, Hikmat Al-Ahmadie, Timothy A. Chan, Ronald Ghossein, Anuradha Gopalan, Douglas A. Levine, Victor Reuter, Samuel Singer, Bhuvanesh Singh, Nguyen Viet Tien, Thomas Broudy, Cyrus Mirsaidi, Praveen Nair, Paul Drwiega, Judy Miller, Jennifer Smith, Howard Zaren, Joong-Won Park, Nguyen Phi Hung, Electron Kebebew, W. Marston Linehan, Adam R. Metwalli, Karel Pacak, Peter A. Pinto, Mark Schiffman, Laura S. Schmidt, Cathy D. Vocke, Nicolas Wentzensen, Robert Worrell, Hannah Yang, Marc Moncrieff, Chandra Goparaju, Jonathan Melamed, Harvey Pass, Natalia Botnariuc, Irina Caraman, Mircea Cernat, Inga Chemencedji, Adrian Clipca, Serghei Doruc, Ghenadie Gorincioi, Sergiu Mura, Maria Pirtac, Irina Stancul, Diana Tcaciuc, Monique Albert, Iakovina Alexopoulou, Angel Arnaout, John Bartlett, Jay Engel, Sebastien Gilbert, Jeremy Parfitt, Harman Sekhon, George Thomas, Doris M. Rassl, Robert C. Rintoul, Carlo Bifulco, Raina Tamakawa, Walter Urba, Nicholas Hayward, Henri Timmers, Anna Antenucci, Francesco Facciolo, Gianluca Grazi, Mirella Marino, Roberta Merola, Ronald de Krijger, Anne-Paule Gimenez-Roqueplo, Alain Piché, Simone Chevalier, Ginette McKercher, Kivanc Birsoy, Gene Barnett, Cathy Brewer, Carol Farver, Theresa Naska, Nathan A. Pennell, Daniel Raymond, Cathy Schilero, Kathy Smolenski, Felicia Williams, Carl Morrison, Jeffrey A. Borgia, Michael J. Liptay, Mark Pool, Christopher W. Seder, Kerstin Junker, Larsson Omberg, Mikhail Dinkin, George Manikhas, Domenico Alvaro, Maria Consiglia Bragazzi, Vincenzo Cardinale, Guido Carpino, Eugenio Gaudio, David Chesla, Sandra Cottingham, Michael Dubina, Fedor Moiseenko, Renumathy Dhanasekaran, Karl-Friedrich Becker, Klaus-Peter Janssen, Julia Slotta-Huspenina, Mohamed H. Abdel-Rahman, Dina Aziz, Sue Bell, Colleen M. Cebulla, Amy Davis, Rebecca Duell, J. Bradley Elder, Joe Hilty, Bahavna Kumar, James Lang, Norman L. Lehman, Randy Mandt, Phuong Nguyen, Robert Pilarski, Karan Rai, Lynn Schoenfield, Kelly Senecal, Paul Wakely, Paul Hansen, Ronald Lechan, James Powers, Arthur Tischler, William E. Grizzle, Katherine C. Sexton, Alison Kastl, Joel Henderson, Sima Porten, Jens Waldmann, Martin Fassnacht, Sylvia L. Asa, Dirk Schadendorf, Marta Couce, Markus Graefen, Hartwig Huland, Guido Sauter, Thorsten Schlomm, Ronald Simon, Pierre Tennstedt, Oluwole Olabode, Mark Nelson, Oliver Bathe, Peter R. Carroll, June M. Chan, Philip Disaia, Pat Glenn, Robin K. Kelley, Charles N. Landen, Joanna Phillips, Michael Prados, Jeffry Simko, Karen Smith-McCune, Scott VandenBerg, Kevin Roggin, Ashley Fehrenbach, Ady Kendler, Suzanne Sifri, Ruth Steele, Antonio Jimeno, Francis Carey, Ian Forgie, Massimo Mannelli, Michael Carney, Brenda Hernandez, Benito Campos, Christel Herold-Mende, Christin Jungk, Andreas Unterberg, Andreas von Deimling, Aaron Bossler, Joseph Galbraith, Laura Jacobus, Michael Knudson, Tina Knutson, Deqin Ma, Mohammed Milhem, Rita Sigmund, Andrew K. Godwin, Rashna Madan, Howard G. Rosenthal, Clement Adebamowo, Sally N. Adebamowo, Alex Boussioutas, David Beer, Thomas Giordano, Anne-Marie Mes-Masson, Fred Saad, Therese Bocklage, Lisa Landrum, Robert Mannel, Kathleen Moore, Katherine Moxley, Russel Postier, Joan Walker, Rosemary Zuna, Michael Feldman, Federico Valdivieso, Rajiv Dhir, James Luketich, Edna M. Mora Pinero, Mario Quintero-Aguilo, Carlos Gilberto Carlotti, Jose Sebastião Dos Santos, Rafael Kemp, Ajith Sankarankuty, Daniela Tirapelli, James Catto, Kathy Agnew, Elizabeth Swisher, Jenette Creaney, Bruce Robinson, Carl Simon Shelley, Eryn M. Godwin, Sara Kendall, Cassaundra Shipman, Carol Bradford, Thomas Carey, Andrea Haddad, Jeffey Moyer, Lisa Peterson, Mark Prince, Laura Rozek, Gregory Wolf, Rayleen Bowman, Kwun M. Fong, Ian Yang, Robert Korst, W. Kimryn Rathmell, J. Leigh Fantacone-Campbell, Jeffrey A. Hooke, Albert J. Kovatich, Craig D. Shriver, John DiPersio, Bettina Drake, Ramaswamy Govindan, Sharon Heath, Timothy Ley, Brian Van Tine, Peter Westervelt, Mark A. Rubin, Jung Il Lee, Natália D. Aredes, Armaz Mariamidze, Thorsson V., Gibbs D.L., Brown S.D., Wolf D., Bortone D.S., Ou Yang T.-H., Porta-Pardo E., Gao G.F., Plaisier C.L., Eddy J.A., Ziv E., Culhane A.C., Paull E.O., Sivakumar I.K.A., Gentles A.J., Malhotra R., Farshidfar F., Colaprico A., Parker J.S., Mose L.E., Vo N.S., Liu J., Liu Y., Rader J., Dhankani V., Reynolds S.M., Bowlby R., Califano A., Cherniack A.D., Anastassiou D., Bedognetti D., Rao A., Chen K., Krasnitz A., Hu H., Malta T.M., Noushmehr H., Pedamallu C.S., Bullman S., Ojesina A.I., Lamb A., Zhou W., Shen H., Choueiri T.K., Weinstein J.N., Guinney J., Saltz J., Holt R.A., Rabkin C.E., Caesar-Johnson S.J., Demchok J.A., Felau I., Kasapi M., Ferguson M.L., Hutter C.M., Sofia H.J., Tarnuzzer R., Wang Z., Yang L., Zenklusen J.C., Zhang J.J., Chudamani S., Lolla L., Naresh R., Pihl T., Sun Q., Wan Y., Wu Y., Cho J., DeFreitas T., Frazer S., Gehlenborg N., Getz G., Heiman D.I., Kim J., Lawrence M.S., Lin P., Meier S., Noble M.S., Saksena G., Voet D., Zhang H., Bernard B., Chambwe N., Knijnenburg T., Kramer R., Leinonen K., Miller M., Reynolds S., Shmulevich I., Zhang W., Akbani R., Broom B.M., Hegde A.M., Ju Z., Kanchi R.S., Korkut A., Li J., Liang H., Ling S., Liu W., Lu Y., Mills G.B., Ng K.-S., Ryan M., Wang J., Zhang J., Abeshouse A., Armenia J., Chakravarty D., Chatila W.K., de Bruijn I., Gao J., Gross B.E., Heins Z.J., Kundra R., La K., Ladanyi M., Luna A., Nissan M.G., Ochoa A., Phillips S.M., Reznik E., Sanchez-Vega F., Sander C., Schultz N., Sheridan R., Sumer S.O., Sun Y., Taylor B.S., Anur P., Peto M., Spellman P., Benz C., Stuart J.M., Wong C.K., Yau C., Hayes D.N., Wilkerson M.D., Ally A., Balasundaram M., Brooks D., Carlsen R., Chuah E., Dhalla N., Jones S.J.M., Kasaian K., Lee D., Ma Y., Marra M.A., Mayo M., Moore R.A., Mungall A.J., Mungall K., Robertson A.G., Sadeghi S., Schein J.E., Sipahimalani P., Tam A., Thiessen N., Tse K., Wong T., Berger A.C., Beroukhim R., Cibulskis C., Gabriel S.B., Ha G., Meyerson M., Schumacher S.E., Shih J., Kucherlapati M.H., Kucherlapati R.S., Baylin S., Cope L., Danilova L., Bootwalla M.S., Lai P.H., Maglinte D.T., Van Den Berg D.J., Weisenberger D.J., Auman J.T., Balu S., Bodenheimer T., Fan C., Hoadley K.A., Hoyle A.P., Jefferys S.R., Jones C.D., Meng S., Mieczkowski P.A., Perou A.H., Perou C.M., Roach J., Shi Y., Simons J.V., Skelly T., Soloway M.G., Tan D., Veluvolu U., Fan H., Hinoue T., Laird P.W., Bellair M., Chang K., Covington K., Creighton C.J., Dinh H., Doddapaneni H., Donehower L.A., Drummond J., Gibbs R.A., Glenn R., Hale W., Han Y., Hu J., Korchina V., Lee S., Lewis L., Li W., Liu X., Morgan M., Morton D., Muzny D., Santibanez J., Sheth M., Shinbrot E., Wang L., Wang M., Wheeler D.A., Xi L., Zhao F., Hess J., Appelbaum E.L., Bailey M., Cordes M.G., Ding L., Fronick C.C., Fulton L.A., Fulton R.S., Kandoth C., Mardis E.R., McLellan M.D., Miller C.A., Schmidt H.K., Wilson R.K., Crain D., Curley E., Gardner J., Lau K., Mallery D., Morris S., Paulauskis J., Penny R., Shelton C., Shelton T., Sherman M., Thompson E., Yena P., Bowen J., Gastier-Foster J.M., Gerken M., Leraas K.M., Lichtenberg T.M., Ramirez N.C., Wise L., Zmuda E., Corcoran N., Costello T., Hovens C., Carvalho A.L., de Carvalho A.C., Fregnani J.H., Longatto-Filho A., Reis R.M., Scapulatempo-Neto C., Silveira H.C.S., Vidal D.O., Burnette A., Eschbacher J., Hermes B., Noss A., Singh R., Anderson M.L., Castro P.D., Ittmann M., Huntsman D., Kohl B., Le X., Thorp R., Andry C., Duffy E.R., Lyadov V., Paklina O., Setdikova G., Shabunin A., Tavobilov M., McPherson C., Warnick R., Berkowitz R., Cramer D., Feltmate C., Horowitz N., Kibel A., Muto M., Raut C.P., Malykh A., Barnholtz-Sloan J.S., Barrett W., Devine K., Fulop J., Ostrom Q.T., Shimmel K., Wolinsky Y., Sloan A.E., De Rose A., Giuliante F., Goodman M., Karlan B.Y., Hagedorn C.H., Eckman J., Harr J., Myers J., Tucker K., Zach L.A., Deyarmin B., Kvecher L., Larson C., Mural R.J., Somiari S., Vicha A., Zelinka T., Bennett J., Iacocca M., Rabeno B., Swanson P., Latour M., Lacombe L., Tetu B., Bergeron A., McGraw M., Staugaitis S.M., Chabot J., Hibshoosh H., Sepulveda A., Su T., Wang T., Potapova O., Voronina O., Desjardins L., Mariani O., Roman-Roman S., Sastre X., Stern M.-H., Cheng F., Signoretti S., Berchuck A., Bigner D., Lipp E., Marks J., McCall S., McLendon R., Secord A., Sharp A., Behera M., Brat D.J., Chen A., Delman K., Force S., Khuri F., Magliocca K., Maithel S., Olson J.J., Owonikoko T., Pickens A., Ramalingam S., Shin D.M., Sica G., Van Meir E.G., Eijckenboom W., Gillis A., Korpershoek E., Looijenga L., Oosterhuis W., Stoop H., van Kessel K.E., Zwarthoff E.C., Calatozzolo C., Cuppini L., Cuzzubbo S., DiMeco F., Finocchiaro G., Mattei L., Perin A., Pollo B., Chen C., Houck J., Lohavanichbutr P., Hartmann A., Stoehr C., Stoehr R., Taubert H., Wach S., Wullich B., Kycler W., Murawa D., Wiznerowicz M., Chung K., Edenfield W.J., Martin J., Baudin E., Bubley G., Bueno R., De Rienzo A., Richards W.G., Kalkanis S., Mikkelsen T., Scarpace L., Girard N., Aymerich M., Campo E., Gine E., Guillermo A.L., Van Bang N., Hanh P.T., Phu B.D., Tang Y., Colman H., Evason K., Dottino P.R., Martignetti J.A., Gabra H., Juhl H., Akeredolu T., Stepa S., Hoon D., Ahn K., Kang K.J., Beuschlein F., Breggia A., Birrer M., Bell D., Borad M., Bryce A.H., Castle E., Chandan V., Cheville J., Copland J.A., Farnell M., Flotte T., Giama N., Ho T., Kendrick M., Kocher J.-P., Kopp K., Moser C., Nagorney D., O'Brien D., O'Neill B.P., Patel T., Petersen G., Que F., Rivera M., Roberts L., Smallridge R., Smyrk T., Stanton M., Thompson R.H., Torbenson M., Yang J.D., Zhang L., Brimo F., Ajani J.A., Gonzalez A.M.A., Behrens C., Bondaruk J., Broaddus R., Czerniak B., Esmaeli B., Fujimoto J., Gershenwald J., Guo C., Lazar A.J., Logothetis C., Meric-Bernstam F., Moran C., Ramondetta L., Rice D., Sood A., Tamboli P., Thompson T., Troncoso P., Tsao A., Wistuba I., Carter C., Haydu L., Hersey P., Jakrot V., Kakavand H., Kefford R., Lee K., Long G., Mann G., Quinn M., Saw R., Scolyer R., Shannon K., Spillane A., Stretch O., Synott M., Thompson J., Wilmott J., Al-Ahmadie H., Chan T.A., Ghossein R., Gopalan A., Levine D.A., Reuter V., Singer S., Singh B., Tien N.V., Broudy T., Mirsaidi C., Nair P., Drwiega P., Miller J., Smith J., Zaren H., Park J.-W., Hung N.P., Kebebew E., Linehan W.M., Metwalli A.R., Pacak K., Pinto P.A., Schiffman M., Schmidt L.S., Vocke C.D., Wentzensen N., Worrell R., Yang H., Moncrieff M., Goparaju C., Melamed J., Pass H., Botnariuc N., Caraman I., Cernat M., Chemencedji I., Clipca A., Doruc S., Gorincioi G., Mura S., Pirtac M., Stancul I., Tcaciuc D., Albert M., Alexopoulou I., Arnaout A., Bartlett J., Engel J., Gilbert S., Parfitt J., Sekhon H., Thomas G., Rassl D.M., Rintoul R.C., Bifulco C., Tamakawa R., Urba W., Hayward N., Timmers H., Antenucci A., Facciolo F., Grazi G., Marino M., Merola R., de Krijger R., Gimenez-Roqueplo A.-P., Piche A., Chevalier S., McKercher G., Birsoy K., Barnett G., Brewer C., Farver C., Naska T., Pennell N.A., Raymond D., Schilero C., Smolenski K., Williams F., Morrison C., Borgia J.A., Liptay M.J., Pool M., Seder C.W., Junker K., Omberg L., Dinkin M., Manikhas G., Alvaro D., Bragazzi M.C., Cardinale V., Carpino G., Gaudio E., Chesla D., Cottingham S., Dubina M., Moiseenko F., Dhanasekaran R., Becker K.-F., Janssen K.-P., Slotta-Huspenina J., Abdel-Rahman M.H., Aziz D., Bell S., Cebulla C.M., Davis A., Duell R., Elder J.B., Hilty J., Kumar B., Lang J., Lehman N.L., Mandt R., Nguyen P., Pilarski R., Rai K., Schoenfield L., Senecal K., Wakely P., Hansen P., Lechan R., Powers J., Tischler A., Grizzle W.E., Sexton K.C., Kastl A., Henderson J., Porten S., Waldmann J., Fassnacht M., Asa S.L., Schadendorf D., Couce M., Graefen M., Huland H., Sauter G., Schlomm T., Simon R., Tennstedt P., Olabode O., Nelson M., Bathe O., Carroll P.R., Chan J.M., Disaia P., Glenn P., Kelley R.K., Landen C.N., Phillips J., Prados M., Simko J., Smith-McCune K., VandenBerg S., Roggin K., Fehrenbach A., Kendler A., Sifri S., Steele R., Jimeno A., Carey F., Forgie I., Mannelli M., Carney M., Hernandez B., Campos B., Herold-Mende C., Jungk C., Unterberg A., von Deimling A., Bossler A., Galbraith J., Jacobus L., Knudson M., Knutson T., Ma D., Milhem M., Sigmund R., Godwin A.K., Madan R., Rosenthal H.G., Adebamowo C., Adebamowo S.N., Boussioutas A., Beer D., Giordano T., Mes-Masson A.-M., Saad F., Bocklage T., Landrum L., Mannel R., Moore K., Moxley K., Postier R., Walker J., Zuna R., Feldman M., Valdivieso F., Dhir R., Luketich J., Pinero E.M.M., Quintero-Aguilo M., Carlotti C.G., Dos Santos J.S., Kemp R., Sankarankuty A., Tirapelli D., Catto J., Agnew K., Swisher E., Creaney J., Robinson B., Shelley C.S., Godwin E.M., Kendall S., Shipman C., Bradford C., Carey T., Haddad A., Moyer J., Peterson L., Prince M., Rozek L., Wolf G., Bowman R., Fong K.M., Yang I., Korst R., Rathmell W.K., Fantacone-Campbell J.L., Hooke J.A., Kovatich A.J., Shriver C.D., DiPersio J., Drake B., Govindan R., Heath S., Ley T., Van Tine B., Westervelt P., Rubin M.A., Lee J.I., Aredes N.D., Mariamidze A., Serody J.S., Demicco E.G., Disis M.L., Vincent B.G., Shmulevich L., SAIC-F-Frederick, Inc, and Leidos Biomedical Research, Inc.
Subjects: Neuroblastoma RAS viral oncogene homolog, Male, 0301 basic medicine, INFORMATION, PREDICTION, Macrophage, medicine.medical_treatment, Lymphocyte, Cell, Cancer Genome Atlas Research Network, COMPREHENSIVE ANALYSIS, computer.software_genre, GENOMIC ANALYSES, 0302 clinical medicine, Transforming Growth Factor beta, Neoplasms, Immunologie, LS2_1, immune subtypes, LS4_6, Immunology and Allergy, tumor immunology, 610 Medicine & health, Child, Th1-Th2 Balance, immunomodulatory, Aged, 80 and over, T-CELL-RECEPTOR, integrative network analysi, cancer genomic, Genomics, Middle Aged, Prognosis, medicine.anatomical_structure, cancer genomics, immuno-oncology, immunotherapy, integrative network analysis, tumor microenvironment, Infectious Diseases, 1107 Immunology, 030220 oncology & carcinogenesis, immune subtype, Female, GENÔMICA, Life Sciences & Biomedicine, Natural language processing, Sentence, Human, Adult, SEQUENCING DATA, Adolescent, Prognosi, Immunology, Cancer immunity, Biology, CLASSIFICATION, Article, NO, Set (abstract data type), Interferon-gamma, Young Adult, 03 medical and health sciences, Immune system, microRNA, REVEALS, medicine, Humans, Epigenetics, Aged, Tumor microenvironment, Wound Healing, Science & Technology, business.industry, REGULATORY NETWORK, Macrophages, Gene sets, Scoring methods, Immunotherapy, SOMATIC MUTATIONS, R package, 030104 developmental biology, Cancer research, Genomic, Artificial intelligence, business, computer
Abstract: We performed an extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA. Across cancer types, we identified six immune subtypes—wound healing, IFN-γ dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-β dominant—characterized by differences in macrophage or lymphocyte signatures, Th1:Th2 cell ratio, extent of intratumoral heterogeneity, aneuploidy, extent of neoantigen load, overall cell proliferation, expression of immunomodulatory genes, and prognosis. Specific driver mutations correlated with lower (CTNNB1, NRAS, or IDH1) or higher (BRAF, TP53, or CASP8) leukocyte levels across all cancers. Multiple control modalities of the intracellular and extracellular networks (transcription, microRNAs, copy number, and epigenetic processes) were involved in tumor-immune cell interactions, both across and within immune subtypes. Our immunogenomics pipeline to characterize these heterogeneous tumors and the resulting data are intended to serve as a resource for future targeted studies to further advance the field. Thorsson et al. present immunogenomics analyses of more than 10,000 tumors, identifying six immune subtypes that encompass multiple cancer types and are hypothesized to define immune response patterns impacting prognosis. This work provides a resource for understanding tumor-immune interactions, with implications for identifying ways to advance research on immunotherapy., 0, info:eu-repo/semantics/published
Published: 2019

29. Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer

Author: Katherine A. Hoadley, Christina Yau, Toshinori Hinoue, Denise M. Wolf, Alexander J. Lazar, Esther Drill, Ronglai Shen, Alison M. Taylor, Andrew D. Cherniack, Vésteinn Thorsson, Rehan Akbani, Reanne Bowlby, Christopher K. Wong, Maciej Wiznerowicz, Francisco Sanchez-Vega, A. Gordon Robertson, Barbara G. Schneider, Michael S. Lawrence, Houtan Noushmehr, Tathiane M. Malta, Joshua M. Stuart, Christopher C. Benz, Peter W. Laird, Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, Gad Getz, David I. Heiman, Jaegil Kim, Pei Lin, Sam Meier, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Yuexin Liu, Michael Miller, Sheila Reynolds, Ilya Shmulevich, Vesteinn Thorsson, Wei Zhang, Bradley M. Broom, Apurva M. Hegde, Zhenlin Ju, Rupa S. Kanchi, Anil Korkut, Jun Li, Han Liang, Shiyun Ling, Wenbin Liu, Yiling Lu, Gordon B. Mills, Kwok-Shing Ng, Arvind Rao, Michael Ryan, Jing Wang, John N. Weinstein, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K. Chatila, Ino de Bruijn, Jianjiong Gao, Benjamin E. Gross, Zachary J. Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G. Nissan, Angelica Ochoa, Sarah M. Phillips, Ed Reznik, Chris Sander, Nikolaus Schultz, Robert Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, D. Neil Hayes, Joel S. Parker, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Ashton C. Berger, Rameen Beroukhim, Carrie Cibulskis, Stacey B. Gabriel, Galen F. Gao, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju S. Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz S. Bootwalla, Phillip H. Lai, Dennis T. Maglinte, David J. Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Cheng Fan, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Amy H. Perou, Charles M. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Huihui Fan, Hui Shen, Wanding Zhou, Michelle Bellair, Kyle Chang, Kyle Covington, Chad J. Creighton, Huyen Dinh, HarshaVardhan Doddapaneni, Lawrence A. Donehower, Jennifer Drummond, Richard A. Gibbs, Robert Glenn, Walker Hale, Yi Han, Jianhong Hu, Viktoriya Korchina, Sandra Lee, Lora Lewis, Wei Li, Xiuping Liu, Margaret Morgan, Donna Morton, Donna Muzny, Jireh Santibanez, Margi Sheth, Eve Shinbrot, Linghua Wang, Min Wang, David A. Wheeler, Liu Xi, Fengmei Zhao, Julian Hess, Elizabeth L. Appelbaum, Matthew Bailey, Matthew G. Cordes, Li Ding, Catrina C. Fronick, Lucinda A. Fulton, Robert S. Fulton, Cyriac Kandoth, Elaine R. Mardis, Michael D. McLellan, Christopher A. Miller, Heather K. Schmidt, Richard K. Wilson, Daniel Crain, Erin Curley, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Mark Sherman, Eric Thompson, Peggy Yena, Jay Bowen, Julie M. Gastier-Foster, Mark Gerken, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Niall Corcoran, Tony Costello, Christopher Hovens, Andre L. Carvalho, Ana C. de Carvalho, José H. Fregnani, Adhemar Longatto-Filho, Rui M. Reis, Cristovam Scapulatempo-Neto, Henrique C.S. Silveira, Daniel O. Vidal, Andrew Burnette, Jennifer Eschbacher, Beth Hermes, Ardene Noss, Rosy Singh, Matthew L. Anderson, Patricia D. Castro, Michael Ittmann, David Huntsman, Bernard Kohl, Xuan Le, Richard Thorp, Chris Andry, Elizabeth R. Duffy, Vladimir Lyadov, Oxana Paklina, Galiya Setdikova, Alexey Shabunin, Mikhail Tavobilov, Christopher McPherson, Ronald Warnick, Ross Berkowitz, Daniel Cramer, Colleen Feltmate, Neil Horowitz, Adam Kibel, Michael Muto, Chandrajit P. Raut, Andrei Malykh, Jill S. Barnholtz-Sloan, Wendi Barrett, Karen Devine, Jordonna Fulop, Quinn T. Ostrom, Kristen Shimmel, Yingli Wolinsky, Andrew E. Sloan, Agostino De Rose, Felice Giuliante, Marc Goodman, Beth Y. Karlan, Curt H. Hagedorn, John Eckman, Jodi Harr, Jerome Myers, Kelinda Tucker, Leigh Anne Zach, Brenda Deyarmin, Hai Hu, Leonid Kvecher, Caroline Larson, Richard J. Mural, Stella Somiari, Ales Vicha, Tomas Zelinka, Joseph Bennett, Mary Iacocca, Brenda Rabeno, Patricia Swanson, Mathieu Latour, Louis Lacombe, Bernard Têtu, Alain Bergeron, Mary McGraw, Susan M. Staugaitis, John Chabot, Hanina Hibshoosh, Antonia Sepulveda, Tao Su, Timothy Wang, Olga Potapova, Olga Voronina, Laurence Desjardins, Odette Mariani, Sergio Roman-Roman, Xavier Sastre, Marc-Henri Stern, Feixiong Cheng, Sabina Signoretti, Andrew Berchuck, Darell Bigner, Eric Lipp, Jeffrey Marks, Shannon McCall, Roger McLendon, Angeles Secord, Alexis Sharp, Madhusmita Behera, Daniel J. Brat, Amy Chen, Keith Delman, Seth Force, Fadlo Khuri, Kelly Magliocca, Shishir Maithel, Jeffrey J. Olson, Taofeek Owonikoko, Alan Pickens, Suresh Ramalingam, Dong M. Shin, Gabriel Sica, Erwin G. Van Meir, Hongzheng Zhang, Wil Eijckenboom, Ad Gillis, Esther Korpershoek, Leendert Looijenga, Wolter Oosterhuis, Hans Stoop, Kim E. van Kessel, Ellen C. Zwarthoff, Chiara Calatozzolo, Lucia Cuppini, Stefania Cuzzubbo, Francesco DiMeco, Gaetano Finocchiaro, Luca Mattei, Alessandro Perin, Bianca Pollo, Chu Chen, John Houck, Pawadee Lohavanichbutr, Arndt Hartmann, Christine Stoehr, Robert Stoehr, Helge Taubert, Sven Wach, Bernd Wullich, Witold Kycler, Dawid Murawa, Ki Chung, W. Jeffrey Edenfield, Julie Martin, Eric Baudin, Glenn Bubley, Raphael Bueno, Assunta De Rienzo, William G. Richards, Steven Kalkanis, Tom Mikkelsen, Lisa Scarpace, Nicolas Girard, Marta Aymerich, Elias Campo, Eva Giné, Armando López Guillermo, Nguyen Van Bang, Phan Thi Hanh, Bui Duc Phu, Yufang Tang, Howard Colman, Kimberley Evason, Peter R. Dottino, John A. Martignetti, Hani Gabra, Hartmut Juhl, Teniola Akeredolu, Serghei Stepa, Dave Hoon, Keunsoo Ahn, Koo Jeong Kang, Felix Beuschlein, Anne Breggia, Michael Birrer, Debra Bell, Mitesh Borad, Alan H. Bryce, Erik Castle, Vishal Chandan, John Cheville, John A. Copland, Michael Farnell, Thomas Flotte, Nasra Giama, Thai Ho, Michael Kendrick, Jean-Pierre Kocher, Karla Kopp, Catherine Moser, David Nagorney, Daniel O’Brien, Brian Patrick O’Neill, Tushar Patel, Gloria Petersen, Florencia Que, Michael Rivera, Lewis Roberts, Robert Smallridge, Thomas Smyrk, Melissa Stanton, R. Houston Thompson, Michael Torbenson, Ju Dong Yang, Lizhi Zhang, Fadi Brimo, Jaffer A. Ajani, Ana Maria Angulo Gonzalez, Carmen Behrens, olanta Bondaruk, Russell Broaddus, Bogdan Czerniak, Bita Esmaeli, Junya Fujimoto, Jeffrey Gershenwald, Charles Guo, Christopher Logothetis, Funda Meric-Bernstam, Cesar Moran, Lois Ramondetta, David Rice, Anil Sood, Pheroze Tamboli, Timothy Thompson, Patricia Troncoso, Anne Tsao, Ignacio Wistuba, Candace Carter, Lauren Haydu, Peter Hersey, Valerie Jakrot, Hojabr Kakavand, Richard Kefford, Kenneth Lee, Georgina Long, Graham Mann, Michael Quinn, Robyn Saw, Richard Scolyer, Kerwin Shannon, Andrew Spillane, Jonathan Stretch, Maria Synott, John Thompson, James Wilmott, Hikmat Al-Ahmadie, Timothy A. Chan, Ronald Ghossein, Anuradha Gopalan, Douglas A. Levine, Victor Reuter, Samuel Singer, Bhuvanesh Singh, Nguyen Viet Tien, Thomas Broudy, Cyrus Mirsaidi, Praveen Nair, Paul Drwiega, Judy Miller, Jennifer Smith, Howard Zaren, Joong-Won Park, Nguyen Phi Hung, Electron Kebebew, W. Marston Linehan, Adam R. Metwalli, Karel Pacak, Peter A. Pinto, Mark Schiffman, Laura S. Schmidt, Cathy D. Vocke, Nicolas Wentzensen, Robert Worrell, Hannah Yang, Marc Moncrieff, Chandra Goparaju, Jonathan Melamed, Harvey Pass, Natalia Botnariuc, Irina Caraman, Mircea Cernat, Inga Chemencedji, Adrian Clipca, Serghei Doruc, Ghenadie Gorincioi, Sergiu Mura, Maria Pirtac, Irina Stancul, Diana Tcaciuc, Monique Albert, Iakovina Alexopoulou, Angel Arnaout, John Bartlett, Jay Engel, Sebastien Gilbert, Jeremy Parfitt, Harman Sekhon, George Thomas, Doris M. Rassl, Robert C. Rintoul, Carlo Bifulco, Raina Tamakawa, Walter Urba, Nicholas Hayward, Henri Timmers, Anna Antenucci, Francesco Facciolo, Gianluca Grazi, Mirella Marino, Roberta Merola, Ronald de Krijger, Anne-Paule Gimenez-Roqueplo, Alain Piché, Simone Chevalier, Ginette McKercher, Kivanc Birsoy, Gene Barnett, Cathy Brewer, Carol Farver, Theresa Naska, Nathan A. Pennell, Daniel Raymond, Cathy Schilero, Kathy Smolenski, Felicia Williams, Carl Morrison, Jeffrey A. Borgia, Michael J. Liptay, Mark Pool, Christopher W. Seder, Kerstin Junker, Larsson Omberg, Mikhail Dinkin, George Manikhas, Domenico Alvaro, Maria Consiglia Bragazzi, Vincenzo Cardinale, Guido Carpino, Eugenio Gaudio, David Chesla, Sandra Cottingham, Michael Dubina, Fedor Moiseenko, Renumathy Dhanasekaran, Karl-Friedrich Becker, Klaus-Peter Janssen, Julia Slotta-Huspenina, Mohamed H. Abdel-Rahman, Dina Aziz, Sue Bell, Colleen M. Cebulla, Amy Davis, Rebecca Duell, J. Bradley Elder, Joe Hilty, Bahavna Kumar, James Lang, Norman L. Lehman, Randy Mandt, Phuong Nguyen, Robert Pilarski, Karan Rai, Lynn Schoenfield, Kelly Senecal, Paul Wakely, Paul Hansen, Ronald Lechan, James Powers, Arthur Tischler, William E. Grizzle, Katherine C. Sexton, Alison Kastl, Joel Henderson, Sima Porten, Jens Waldmann, Martin Fassnacht, Sylvia L. Asa, Dirk Schadendorf, Marta Couce, Markus Graefen, Hartwig Huland, Guido Sauter, Thorsten Schlomm, Ronald Simon, Pierre Tennstedt, Oluwole Olabode, Mark Nelson, Oliver Bathe, Peter R. Carroll, June M. Chan, Philip Disaia, Pat Glenn, Robin K. Kelley, Charles N. Landen, Joanna Phillips, Michael Prados, Jeffry Simko, Karen Smith-McCune, Scott VandenBerg, Kevin Roggin, Ashley Fehrenbach, Ady Kendler, Suzanne Sifri, Ruth Steele, Antonio Jimeno, Francis Carey, Ian Forgie, Massimo Mannelli, Michael Carney, Brenda Hernandez, Benito Campos, Christel Herold-Mende, Christin Jungk, Andreas Unterberg, Andreas von Deimling, Aaron Bossler, Joseph Galbraith, Laura Jacobus, Michael Knudson, Tina Knutson, Deqin Ma, Mohammed Milhem, Rita Sigmund, Andrew K. Godwin, Rashna Madan, Howard G. Rosenthal, Clement Adebamowo, Sally N. Adebamowo, Alex Boussioutas, David Beer, Thomas Giordano, Anne-Marie Mes-Masson, Fred Saad, Therese Bocklage, Lisa Landrum, Robert Mannel, Kathleen Moore, Katherine Moxley, Russel Postier, Joan Walker, Rosemary Zuna, Michael Feldman, Federico Valdivieso, Rajiv Dhir, James Luketich, Edna M. Mora Pinero, Mario Quintero-Aguilo, Carlos Gilberto Carlotti, Jose Sebastião Dos Santos, Rafael Kemp, Ajith Sankarankuty, Daniela Tirapelli, James Catto, Kathy Agnew, Elizabeth Swisher, Jenette Creaney, Bruce Robinson, Carl Simon Shelley, Eryn M. Godwin, Sara Kendall, Cassaundra Shipman, Carol Bradford, Thomas Carey, Andrea Haddad, Jeffey Moyer, Lisa Peterson, Mark Prince, Laura Rozek, Gregory Wolf, Rayleen Bowman, Kwun M. Fong, Ian Yang, Robert Korst, W. Kimryn Rathmell, J. Leigh Fantacone-Campbell, Jeffrey A. Hooke, Albert J. Kovatich, Craig D. Shriver, John DiPersio, Bettina Drake, Ramaswamy Govindan, Sharon Heath, Timothy Ley, Brian Van Tine, Peter Westervelt, Mark A. Rubin, Jung Il Lee, Natália D. Aredes, Armaz Mariamidze, SAIC-F-Frederick, Inc, Leidos Biomedical Research, Inc., Hoadley K.A., Yau C., Hinoue T., Wolf D.M., Lazar A.J., Drill E., Shen R., Taylor A.M., Cherniack A.D., Thorsson V., Akbani R., Bowlby R., Wong C.K., Wiznerowicz M., Sanchez-Vega F., Robertson A.G., Schneider B.G., Lawrence M.S., Noushmehr H., Malta T.M., Caesar-Johnson S.J., Demchok J.A., Felau I., Kasapi M., Ferguson M.L., Hutter C.M., Sofia H.J., Tarnuzzer R., Wang Z., Yang L., Zenklusen J.C., Zhang J.J., Chudamani S., Liu J., Lolla L., Naresh R., Pihl T., Sun Q., Wan Y., Wu Y., Cho J., DeFreitas T., Frazer S., Gehlenborg N., Getz G., Heiman D.I., Kim J., Lin P., Meier S., Noble M.S., Saksena G., Voet D., Zhang H., Bernard B., Chambwe N., Dhankani V., Knijnenburg T., Kramer R., Leinonen K., Liu Y., Miller M., Reynolds S., Shmulevich I., Zhang W., Broom B.M., Hegde A.M., Ju Z., Kanchi R.S., Korkut A., Li J., Liang H., Ling S., Liu W., Lu Y., Mills G.B., Ng K.-S., Rao A., Ryan M., Wang J., Weinstein 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Mose L.E., Perou A.H., Perou C.M., Roach J., Shi Y., Simons J.V., Skelly T., Soloway M.G., Tan D., Veluvolu U., Fan H., Laird P.W., Shen H., Zhou W., Bellair M., Chang K., Covington K., Creighton C.J., Dinh H., Doddapaneni H., Donehower L.A., Drummond J., Gibbs R.A., Glenn R., Hale W., Han Y., Hu J., Korchina V., Lee S., Lewis L., Li W., Liu X., Morgan M., Morton D., Muzny D., Santibanez J., Sheth M., Shinbrot E., Wang L., Wang M., Wheeler D.A., Xi L., Zhao F., Hess J., Appelbaum E.L., Bailey M., Cordes M.G., Ding L., Fronick C.C., Fulton L.A., Fulton R.S., Kandoth C., Mardis E.R., McLellan M.D., Miller C.A., Schmidt H.K., Wilson R.K., Crain D., Curley E., Gardner J., Lau K., Mallery D., Morris S., Paulauskis J., Penny R., Shelton C., Shelton T., Sherman M., Thompson E., Yena P., Bowen J., Gastier-Foster J.M., Gerken M., Leraas K.M., Lichtenberg T.M., Ramirez N.C., Wise L., Zmuda E., Corcoran N., Costello T., Hovens C., Carvalho A.L., de Carvalho A.C., Fregnani J.H., Longatto-Filho A., Reis R.M., Scapulatempo-Neto C., Silveira H.C.S., Vidal D.O., Burnette A., Eschbacher J., Hermes B., Noss A., Singh R., Anderson M.L., Castro P.D., Ittmann M., Huntsman D., Kohl B., Le X., Thorp R., Andry C., Duffy E.R., Lyadov V., Paklina O., Setdikova G., Shabunin A., Tavobilov M., McPherson C., Warnick R., Berkowitz R., Cramer D., Feltmate C., Horowitz N., Kibel A., Muto M., Raut C.P., Malykh A., Barnholtz-Sloan J.S., Barrett W., Devine K., Fulop J., Ostrom Q.T., Shimmel K., Wolinsky Y., Sloan A.E., De Rose A., Giuliante F., Goodman M., Karlan B.Y., Hagedorn C.H., Eckman J., Harr J., Myers J., Tucker K., Zach L.A., Deyarmin B., Hu H., Kvecher L., Larson C., Mural R.J., Somiari S., Vicha A., Zelinka T., Bennett J., Iacocca M., Rabeno B., Swanson P., Latour M., Lacombe L., Tetu B., Bergeron A., McGraw M., Staugaitis S.M., Chabot J., Hibshoosh H., Sepulveda A., Su T., Wang T., Potapova O., Voronina O., Desjardins L., Mariani O., Roman-Roman S., Sastre X., Stern M.-H., Cheng F., 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J., Smith J., Zaren H., Park J.-W., Hung N.P., Kebebew E., Linehan W.M., Metwalli A.R., Pacak K., Pinto P.A., Schiffman M., Schmidt L.S., Vocke C.D., Wentzensen N., Worrell R., Yang H., Moncrieff M., Goparaju C., Melamed J., Pass H., Botnariuc N., Caraman I., Cernat M., Chemencedji I., Clipca A., Doruc S., Gorincioi G., Mura S., Pirtac M., Stancul I., Tcaciuc D., Albert M., Alexopoulou I., Arnaout A., Bartlett J., Engel J., Gilbert S., Parfitt J., Sekhon H., Thomas G., Rassl D.M., Rintoul R.C., Bifulco C., Tamakawa R., Urba W., Hayward N., Timmers H., Antenucci A., Facciolo F., Grazi G., Marino M., Merola R., de Krijger R., Gimenez-Roqueplo A.-P., Piche A., Chevalier S., McKercher G., Birsoy K., Barnett G., Brewer C., Farver C., Naska T., Pennell N.A., Raymond D., Schilero C., Smolenski K., Williams F., Morrison C., Borgia J.A., Liptay M.J., Pool M., Seder C.W., Junker K., Omberg L., Dinkin M., Manikhas G., Alvaro D., Bragazzi M.C., Cardinale V., Carpino G., Gaudio E., Chesla D., Cottingham S., Dubina M., Moiseenko F., Dhanasekaran R., Becker K.-F., Janssen K.-P., Slotta-Huspenina J., Abdel-Rahman M.H., Aziz D., Bell S., Cebulla C.M., Davis A., Duell R., Elder J.B., Hilty J., Kumar B., Lang J., Lehman N.L., Mandt R., Nguyen P., Pilarski R., Rai K., Schoenfield L., Senecal K., Wakely P., Hansen P., Lechan R., Powers J., Tischler A., Grizzle W.E., Sexton K.C., Kastl A., Henderson J., Porten S., Waldmann J., Fassnacht M., Asa S.L., Schadendorf D., Couce M., Graefen M., Huland H., Sauter G., Schlomm T., Simon R., Tennstedt P., Olabode O., Nelson M., Bathe O., Carroll P.R., Chan J.M., Disaia P., Glenn P., Kelley R.K., Landen C.N., Phillips J., Prados M., Simko J., Smith-McCune K., VandenBerg S., Roggin K., Fehrenbach A., Kendler A., Sifri S., Steele R., Jimeno A., Carey F., Forgie I., Mannelli M., Carney M., Hernandez B., Campos B., Herold-Mende C., Jungk C., Unterberg A., von Deimling A., Bossler A., Galbraith J., Jacobus L., Knudson M., Knutson T., Ma D., Milhem M., Sigmund R., Godwin A.K., Madan R., Rosenthal H.G., Adebamowo C., Adebamowo S.N., Boussioutas A., Beer D., Giordano T., Mes-Masson A.-M., Saad F., Bocklage T., Landrum L., Mannel R., Moore K., Moxley K., Postier R., Walker J., Zuna R., Feldman M., Valdivieso F., Dhir R., Luketich J., Pinero E.M.M., Quintero-Aguilo M., Carlotti C.G., Dos Santos J.S., Kemp R., Sankarankuty A., Tirapelli D., Catto J., Agnew K., Swisher E., Creaney J., Robinson B., Shelley C.S., Godwin E.M., Kendall S., Shipman C., Bradford C., Carey T., Haddad A., Moyer J., Peterson L., Prince M., Rozek L., Wolf G., Bowman R., Fong K.M., Yang I., Korst R., Rathmell W.K., Fantacone-Campbell J.L., Hooke J.A., Kovatich A.J., Shriver C.D., DiPersio J., Drake B., Govindan R., Heath S., Ley T., Van Tine B., Westervelt P., Rubin M.A., Lee J.I., Aredes N.D., Mariamidze A., and Benz C.C.
Subjects: 0301 basic medicine, Databases, Factual, Aneuploidy, methylome, Biochemistry, Genome, Transcriptome, Neoplasms, Cancer Genome Atlas Network, LS2_1, LS4_6, Cluster Analysis, INTEGRATED GENOMIC CHARACTERIZATION, 11 Medical and Health Sciences, subtypes, SIGNATURE, cell-of-origin, MicroRNA, 3. Good health, Neoplasm Proteins, UNKNOWN PRIMARY, Proteome, DNA methylation, ACCURATE, Life Sciences & Biomedicine, Human, Cell type, Biochemistry & Molecular Biology, proteome, 610 Medicine & health, Computational biology, Biology, MUTAÇÃO, Chromosome, BREAST, General Biochemistry, Genetics and Molecular Biology, Article, Chromosomes, NO, subtype, Neoplasm Protein, 03 medical and health sciences, microRNA, medicine, organ, cancer, Humans, tissues, RNA, Messenger, genome, Cluster Analysi, Science & Technology, Biochemistry, Genetics and Molecular Biology(all), Gene Expression Profiling, tissue, Cell Biology, organs, TCGA, transcriptome, 06 Biological Sciences, DNA Methylation, medicine.disease, SIMILARITIES, MicroRNAs, 030104 developmental biology, DISCOVERY, Mutation, Neoplasm, Human genome, CpG Islands, CpG Island, Genetics and Molecular Biology(all), Developmental Biology
Abstract: SUMMARY We conducted comprehensive integrative molecular analyses of the complete set of tumors in The Cancer Genome Atlas (TCGA), consisting of approximately 10,000 specimens and representing 33 types of cancer. We performed molecular clustering using data on chromosome-arm-level aneuploidy, DNA hypermethylation, mRNA, and miRNA expression levels and reverse-phase protein arrays, of which all, except for aneuploidy, revealed clustering primarily organized by histology, tissue type, or anatomic origin. The influence of cell type was evident in DNA-methylation-based clustering, even after excluding sites with known preexisting tissue-type-specific methylation. Integrative clustering further emphasized the dominant role of cell-of-origin patterns. Molecular similarities among histologically or anatomically related cancer types provide a basis for focused pan-cancer analyses, such as pan-gastrointestinal, pan-gynecological, pan-kidney, and pan-squamous cancers, and those related by stemness features, which in turn may inform strategies for future therapeutic development., In Brief Comprehensive, integrated molecular analysis identifies molecular relationships across a large diverse set of human cancers, suggesting future directions for exploring clinical actionability in cancer treatment.
Published: 2017

30. The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

Author: Christopher J. Ricketts, Aguirre A. De Cubas, Huihui Fan, Christof C. Smith, Martin Lang, Ed Reznik, Reanne Bowlby, Ewan A. Gibb, Rehan Akbani, Rameen Beroukhim, Donald P. Bottaro, Toni K. Choueiri, Richard A. Gibbs, Andrew K. Godwin, Scott Haake, A. Ari Hakimi, Elizabeth P. Henske, James J. Hsieh, Thai H. Ho, Rupa S. Kanchi, Bhavani Krishnan, David J. Kwiatkowski, Wembin Lui, Maria J. Merino, Gordon B. Mills, Jerome Myers, Michael L. Nickerson, Victor E. Reuter, Laura S. Schmidt, C. Simon Shelley, Hui Shen, Brian Shuch, Sabina Signoretti, Ramaprasad Srinivasan, Pheroze Tamboli, George Thomas, Benjamin G. Vincent, Cathy D. Vocke, David A. Wheeler, Lixing Yang, William Y. Kim, A. Gordon Robertson, Paul T. Spellman, W. Kimryn Rathmell, W. Marston Linehan, Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, Gad Getz, David I. Heiman, Jaegil Kim, Michael S. Lawrence, Pei Lin, Sam Meier, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Yuexin Liu, Michael Miller, Sheila Reynolds, Ilya Shmulevich, Vesteinn Thorsson, Wei Zhang, Bradley M. Broom, Apurva M. Hegde, Zhenlin Ju, Anil Korkut, Jun Li, Han Liang, Shiyun Ling, Wenbin Liu, Yiling Lu, Kwok-Shing Ng, Arvind Rao, Michael Ryan, Jing Wang, John N. Weinstein, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K. Chatila, Ino de Bruijn, Jianjiong Gao, Benjamin E. Gross, Zachary J. Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G. Nissan, Angelica Ochoa, Sarah M. Phillips, Francisco Sanchez-Vega, Chris Sander, Nikolaus Schultz, Robert Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, Joshua M. Stuart, Christopher K. Wong, Christina Yau, D. Neil Hayes, Joel S. Parker, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Ashton C. Berger, Andrew D. Cherniack, Carrie Cibulskis, Stacey B. Gabriel, Galen F. Gao, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju S. Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz S. Bootwalla, Phillip H. Lai, Dennis T. Maglinte, David J. Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Cheng Fan, Katherine A. Hoadley, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Amy H. Perou, Charles M. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Toshinori Hinoue, Peter W. Laird, Wanding Zhou, Michelle Bellair, Kyle Chang, Kyle Covington, Chad J. Creighton, Huyen Dinh, HarshaVardhan Doddapaneni, Lawrence A. Donehower, Jennifer Drummond, Robert Glenn, Walker Hale, Yi Han, Jianhong Hu, Viktoriya Korchina, Sandra Lee, Lora Lewis, Wei Li, Xiuping Liu, Margaret Morgan, Donna Morton, Donna Muzny, Jireh Santibanez, Margi Sheth, Eve Shinbrot, Linghua Wang, Min Wang, Liu Xi, Fengmei Zhao, Julian Hess, Elizabeth L. Appelbaum, Matthew Bailey, Matthew G. Cordes, Li Ding, Catrina C. Fronick, Lucinda A. Fulton, Robert S. Fulton, Cyriac Kandoth, Elaine R. Mardis, Michael D. McLellan, Christopher A. Miller, Heather K. Schmidt, Richard K. Wilson, Daniel Crain, Erin Curley, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Mark Sherman, Eric Thompson, Peggy Yena, Jay Bowen, Julie M. Gastier-Foster, Mark Gerken, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Niall Corcoran, Tony Costello, Christopher Hovens, Andre L. Carvalho, Ana C. de Carvalho, José H. Fregnani, Adhemar Longatto-Filho, Rui M. Reis, Cristovam Scapulatempo-Neto, Henrique C.S. Silveira, Daniel O. Vidal, Andrew Burnette, Jennifer Eschbacher, Beth Hermes, Ardene Noss, Rosy Singh, Matthew L. Anderson, Patricia D. Castro, Michael Ittmann, David Huntsman, Bernard Kohl, Xuan Le, Richard Thorp, Chris Andry, Elizabeth R. 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Aredes, Armaz Mariamidze, SAIC-F-Frederick, Inc, Leidos Biomedical Research, Inc., Ricketts C.J., De Cubas A.A., Fan H., Smith C.C., Lang M., Reznik E., Bowlby R., Gibb E.A., Akbani R., Beroukhim R., Bottaro D.P., Choueiri T.K., Gibbs R.A., Godwin A.K., Haake S., Hakimi A.A., Henske E.P., Hsieh J.J., Ho T.H., Kanchi R.S., Krishnan B., Kwaitkowski D.J., Lui W., Merino M.J., Mills G.B., Myers J., Nickerson M.L., Reuter V.E., Schmidt L.S., Shelley C.S., Shen H., Shuch B., Signoretti S., Srinivasan R., Tamboli P., Thomas G., Vincent B.G., Vocke C.D., Wheeler D.A., Yang L., Kim W.T., Robertson A.G., Caesar-Johnson S.J., Demchok J.A., Felau I., Kasapi M., Ferguson M.L., Hutter C.M., Sofia H.J., Tarnuzzer R., Wang Z., Zenklusen J.C., Zhang J.J., Chudamani S., Liu J., Lolla L., Naresh R., Pihl T., Sun Q., Wan Y., Wu Y., Cho J., DeFreitas T., Frazer S., Gehlenborg N., Getz G., Heiman D.I., Kim J., Lawrence M.S., Lin P., Meier S., Noble M.S., Saksena G., Voet D., Zhang H., Bernard B., Chambwe 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J.I., Aredes N.D., and Mariamidze A.
Subjects: Genetics and Molecular Biology (all), 0301 basic medicine, Transcription Factor, Chromophobe Renal Cell Carcinoma, papillary renal cell carcinoma, Cell, Cancer Genome Atlas Research Network, Chromophobe cell, clear cell renal cell carcinoma, urologic and male genital diseases, Biochemistry, PBRM1, chromatin remodeling, CDKN2A, chromophobe renal cell carcinoma, DNA hypermethylation, immune signature, PanCanAtlas, TCGA, 0302 clinical medicine, Renal cell carcinoma, LS2_1, LS4_6, Biochemistry, Genetics and Molecular Biology (all), RNA-SEQ, SOMATIC POINT MUTATIONS, CLASS DISCOVERY, lcsh:QH301-705.5, Nuclear Protein, BAP1, Papillary renal cell carcinomas, KIDNEY CANCER, Kidney Neoplasm, Nuclear Proteins, female genital diseases and pregnancy complications, Kidney Neoplasms, 3. Good health, DNA-Binding Proteins, medicine.anatomical_structure, Phenotype, 030220 oncology & carcinogenesis, Survival Analysi, MESSENGER-RNA, Life Sciences & Biomedicine, Ubiquitin Thiolesterase, Metabolic Networks and Pathways, Human, EXPRESSION, SEQUENCING DATA, GENETIC-BASIS, 610 Medicine & health, Computational biology, Biology, BREAST, Article, General Biochemistry, Genetics and Molecular Biology, NO, 03 medical and health sciences, Atlas (anatomy), Cancer genome, medicine, Biomarkers, Tumor, Humans, ESTRATÉGIAS TERAPÊUTICAS, neoplasms, Carcinoma, Renal Cell, Cyclin-Dependent Kinase Inhibitor p16, Tumor Suppressor Protein, Science & Technology, Biochemistry, Genetics and Molecular Biology(all), Genome, Human, Tumor Suppressor Proteins, PTEN Phosphohydrolase, Metabolic Networks and Pathway, Cell Biology, DNA, medicine.disease, Survival Analysis, Clear cell renal cell carcinoma, 030104 developmental biology, lcsh:Biology (General), Cancer research, PanCanAtla, Genetics and Molecular Biology(all), Transcription Factors
Abstract: SUMMARY Renal cell carcinoma (RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD) ChRCC that associated with extremely poor survival., Graphical abstract In Brief Ricketts et al. find distinctive features of each RCC subtype, providing the foundation for development of subtypespecific therapeutic and management strategies. Somatic alteration of BAP1, PBRM1, and metabolic pathways correlates with subtype-specific decreased survival, while CDKN2A alteration, DNA hypermethylation, and Th2 immune signature correlate with decreased survival within all subtypes.
Published: 2017

31. lncRNA Epigenetic Landscape Analysis Identifies EPIC1 as an Oncogenic lncRNA that Interacts with MYC and Promotes Cell-Cycle Progression in Cancer

Author: Zehua Wang, Bo Yang, Min Zhang, Weiwei Guo, Zhiyuan Wu, Yue Wang, Lin Jia, Song Li, Wen Xie, Da Yang, Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, Gad Getz, David I. Heiman, Jaegil Kim, Michael S. Lawrence, Pei Lin, Sam Meier, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Yuexin Liu, Michael Miller, Sheila Reynolds, Ilya Shmulevich, Vesteinn Thorsson, Wei Zhang, Rehan Akbani, Bradley M. Broom, Apurva M. Hegde, Zhenlin Ju, Rupa S. Kanchi, Anil Korkut, Jun Li, Han Liang, Shiyun Ling, Wenbin Liu, Yiling Lu, Gordon B. Mills, Kwok-Shing Ng, Arvind Rao, Michael Ryan, Jing Wang, John N. Weinstein, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K. Chatila, Inode Bruijn, Jianjiong Gao, Benjamin E. Gross, Zachary J. Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G. Nissan, Angelica Ochoa, Sarah M. Phillips, Ed Reznik, Francisco Sanchez-Vega, Chris Sander, Nikolaus Schultz, Robert Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, Joshua M. Stuart, Christopher K. Wong, Christina Yau, D. Neil Hayes, Joel S. Parker, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, A. Gordon Robertson, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Ashton C. Berger, Rameen Beroukhim, Andrew D. Cherniack, Carrie Cibulskis, Stacey B. Gabriel, Galen F. Gao, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju S. Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz S. Bootwalla, Phillip H. Lai, Dennis T. Maglinte, David J. Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Cheng Fan, Katherine A. Hoadley, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Amy H. Perou, Charles M. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Huihui Fan, Toshinori Hinoue, Peter W. Laird, Hui Shen, Wanding Zhou, Michelle Bellair, Kyle Chang, Kyle Covington, Chad J. Creighton, Huyen Dinh, HarshaVardhan Doddapaneni, Lawrence A. Donehower, Jennifer Drummond, Richard A. 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Subjects: 0301 basic medicine, breast cancer, CIMP, ENSG00000224271, EPIC1, LOC284930, long noncoding RNA, MYC, P21, TCGA pan-cancer, Cancer Research, PROTEIN, Cancer Genome Atlas Research Network, medicine.disease_cause, ANALYSES REVEAL, Epigenesis, Genetic, Mice, LS2_1, LS4_6, 610 Medicine & health, Promoter Regions, Genetic, GENE-EXPRESSION, Regulation of gene expression, FENÓTIPOS, Cell Cycle, METHYLATION, Cell cycle, Prognosis, Long non-coding RNA, Up-Regulation, TRANSCRIPTIONAL NETWORK, GENOME, Gene Expression Regulation, Neoplastic, SEQ, CpG site, Oncology, DNA methylation, Female, RNA, Long Noncoding, Life Sciences & Biomedicine, Breast Neoplasm, Human, Prognosi, Breast Neoplasms, Biology, BINDING-SITES, Article, NO, Proto-Oncogene Proteins c-myc, 03 medical and health sciences, Cell Line, Tumor, medicine, C-MYC, Animals, Humans, 1112 Oncology and Carcinogenesis, Epigenetics, Oncology & Carcinogenesis, Science & Technology, Binding Sites, Animal, Binding Site, Cancer, Cell Biology, DNA Methylation, medicine.disease, 030104 developmental biology, Cancer research, CpG Islands, CpG Island, Carcinogenesis, 1109 Neurosciences, Neoplasm Transplantation
Abstract: We characterized the epigenetic landscape of genes encoding long noncoding RNAs (lncRNAs) across 6,475 tumors and 455 cancer cell lines. In stark contrast to the CpG island hypermethylation phenotype in cancer, we observed a recurrent hypomethylation of 1,006 lncRNA genes in cancer, including EPIC1 (epigenetically-induced lncRNA1). Overexpression of EPIC1 is associated with poor prognosis in luminal B breast cancer patients and enhances tumor growth in vitro and in vivo. Mechanistically, EPIC1 promotes cell-cycle progression by interacting with MYC through EPIC1's 129–283 nt region. EPIC1 knockdown reduces the occupancy of MYC to its target genes (e.g., CDKN1A, CCNA2, CDC20, and CDC45). MYC depletion abolishes EPIC1's regulation of MYC target and luminal breast cancer tumorigenesis in vitro and in vivo. Wang et al. characterize the epigenetic landscape of lncRNAs genes across a large number of human tumors and cancer cell lines and observe recurrent hypomethylation of lncRNA genes, including EPIC1. EPIC1 RNA promotes cell-cycle progression by interacting with MYC and enhancing its binding to target genes.
Published: 2018

32. Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation

Author: Tathiane M. Malta, Artem Sokolov, Andrew J. Gentles, Tomasz Burzykowski, Laila Poisson, John N. Weinstein, Bożena Kamińska, Joerg Huelsken, Larsson Omberg, Olivier Gevaert, Antonio Colaprico, Patrycja Czerwińska, Sylwia Mazurek, Lopa Mishra, Holger Heyn, Alex Krasnitz, Andrew K. Godwin, Alexander J. Lazar, Joshua M. Stuart, Katherine A. Hoadley, Peter W. Laird, Houtan Noushmehr, Maciej Wiznerowicz, Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, Gad Getz, David I. Heiman, Jaegil Kim, Michael S. Lawrence, Pei Lin, Sam Meier, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Yuexin Liu, Michael Miller, Sheila Reynolds, Ilya Shmulevich, Vesteinn Thorsson, Wei Zhang, Rehan Akbani, Bradley M. Broom, Apurva M. Hegde, Zhenlin Ju, Rupa S. Kanchi, Anil Korkut, Jun Li, Han Liang, Shiyun Ling, Wenbin Liu, Yiling Lu, Gordon B. Mills, Kwok-Shing Ng, Arvind Rao, Michael Ryan, Jing Wang, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K. Chatila, Ino de Bruijn, Jianjiong Gao, Benjamin E. Gross, Zachary J. Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G. Nissan, Angelica Ochoa, Sarah M. Phillips, Ed Reznik, Francisco Sanchez-Vega, Chris Sander, Nikolaus Schultz, Robert Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, Christopher K. Wong, Christina Yau, D. Neil Hayes, Joel S. Parker, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, A. Gordon Robertson, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Ashton C. Berger, Rameen Beroukhim, Andrew D. Cherniack, Carrie Cibulskis, Stacey B. Gabriel, Galen F. Gao, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju S. Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz S. Bootwalla, Phillip H. Lai, Dennis T. Maglinte, David J. Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Cheng Fan, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Amy H. Perou, Charles M. 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Wilson, Daniel Crain, Erin Curley, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Mark Sherman, Eric Thompson, Peggy Yena, Jay Bowen, Julie M. Gastier-Foster, Mark Gerken, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Niall Corcoran, Tony Costello, Christopher Hovens, Andre L. Carvalho, Ana C. de Carvalho, José H. Fregnani, Adhemar Longatto-Filho, Rui M. Reis, Cristovam Scapulatempo-Neto, Henrique C.S. Silveira, Daniel O. Vidal, Andrew Burnette, Jennifer Eschbacher, Beth Hermes, Ardene Noss, Rosy Singh, Matthew L. Anderson, Patricia D. Castro, Michael Ittmann, David Huntsman, Bernard Kohl, Xuan Le, Richard Thorp, Chris Andry, Elizabeth R. Duffy, Vladimir Lyadov, Oxana Paklina, Galiya Setdikova, Alexey Shabunin, Mikhail Tavobilov, Christopher McPherson, Ronald Warnick, Ross Berkowitz, Daniel Cramer, Colleen Feltmate, Neil Horowitz, Adam Kibel, Michael Muto, Chandrajit P. 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Subjects: 0301 basic medicine, Carcinogenesis, pan-cancer, Cancer Genome Atlas Research Network, medicine.disease_cause, Biochemistry, epigenomic, Epigenesis, Genetic, genomic, Machine Learning, GENE-EXPRESSION SIGNATURE, TUMOR, Neoplasms, Databases, Genetic, Tumor Microenvironment, LS4_6, Stemness, Neoplasm Metastasis, 610 Medicine & health, Induced pluripotent stem cell, 11 Medical and Health Sciences, Carcinogenesi, Epigenomics, Cancer stem cells, Stem Cells, PROLIFERATION, MicroRNA, Sciences bio-médicales et agricoles, CANCER, stemne, Neoplasm Metastasi, CONNECTIVITY MAP, ALGORITMOS, Stem cell, Life Sciences & Biomedicine, Human, Biochemistry & Molecular Biology, cancer stem cell, The Cancer Genome Atlas, Biology, Article, General Biochemistry, Genetics and Molecular Biology, NO, ANNEXIN 1, 03 medical and health sciences, Stem Cell, Cancer stem cell, medicine, Humans, Epigenetics, EMBRYONIC STEM, Tumor microenvironment, Science & Technology, Biochemistry, Genetics and Molecular Biology(all), dedifferentiation, Cell Biology, 06 Biological Sciences, Cell Dedifferentiation, DNA Methylation, Immune checkpoint, SELF-RENEWAL, MicroRNAs, 030104 developmental biology, CELLS, Cancer research, Neoplasm, OVEREXPRESSION, The Cancer Genome Atla, Transcriptome, cancer stem cells, machine learning, stemness, Genetics and Molecular Biology(all), Developmental Biology
Abstract: Cancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem-cell-like features. Here, we provide novel stemness indices for assessing the degree of oncogenic dedifferentiation. We used an innovative one-class logistic regression (OCLR) machine-learning algorithm to extract transcriptomic and epigenetic feature sets derived from non-transformed pluripotent stem cells and their differentiated progeny. Using OCLR, we were able to identify previously undiscovered biological mechanisms associated with the dedifferentiated oncogenic state. Analyses of the tumor microenvironment revealed unanticipated correlation of cancer stemness with immune checkpoint expression and infiltrating immune cells. We found that the dedifferentiated oncogenic phenotype was generally most prominent in metastatic tumors. Application of our stemness indices to single-cell data revealed patterns of intra-tumor molecular heterogeneity. Finally, the indices allowed for the identification of novel targets and possible targeted therapies aimed at tumor differentiation. Stemness features extracted from transcriptomic and epigenetic data from TCGA tumors reveal novel biological and clinical insight, as well as potential drug targets for anti-cancer therapies., 0, info:eu-repo/semantics/published
Published: 2018

33. Comprehensive Molecular Characterization of the Hippo Signaling Pathway in Cancer

Author: Yumeng Wang, Xiaoyan Xu, Dejan Maglic, Michael T. Dill, Kamalika Mojumdar, Patrick Kwok-Shing Ng, Kang Jin Jeong, Yiu Huen Tsang, Daniela Moreno, Venkata Hemanjani Bhavana, Xinxin Peng, Zhongqi Ge, Hu Chen, Jun Li, Zhongyuan Chen, Huiwen Zhang, Leng Han, Di Du, Chad J. Creighton, Gordon B. Mills, Fernando Camargo, Han Liang, Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, Gad Getz, David I. Heiman, Jaegil Kim, Michael S. Lawrence, Pei Lin, Sam Meier, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Yuexin Liu, Michael Miller, Sheila Reynolds, Ilya Shmulevich, Vesteinn Thorsson, Wei Zhang, Rehan Akbani, Bradley M. Broom, Apurva M. Hegde, Zhenlin Ju, Rupa S. Kanchi, Anil Korkut, Shiyun Ling, Wenbin Liu, Yiling Lu, Kwok-Shing Ng, Arvind Rao, Michael Ryan, Jing Wang, John N. Weinstein, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K. Chatila, Ino de Bruijn, Jianjiong Gao, Benjamin E. Gross, Zachary J. Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G. Nissan, Angelica Ochoa, Sarah M. Phillips, Ed Reznik, Francisco Sanchez-Vega, Chris Sander, Nikolaus Schultz, Robert Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, Joshua M. Stuart, Christopher K. Wong, Christina Yau, D. Neil Hayes, Joel S. Parker, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, A. Gordon Robertson, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Ashton C. Berger, Rameen Beroukhim, Andrew D. Cherniack, Carrie Cibulskis, Stacey B. Gabriel, Galen F. Gao, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju S. Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz S. Bootwalla, Phillip H. Lai, Dennis T. Maglinte, David J. Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Cheng Fan, Katherine A. Hoadley, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Amy H. Perou, Charles M. 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Wilson, Daniel Crain, Erin Curley, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Mark Sherman, Eric Thompson, Peggy Yena, Jay Bowen, Julie M. Gastier-Foster, Mark Gerken, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Niall Corcoran, Tony Costello, Christopher Hovens, Andre L. Carvalho, Ana C. de Carvalho, José H. Fregnani, Adhemar Longatto-Filho, Rui M. Reis, Cristovam Scapulatempo-Neto, Henrique C.S. Silveira, Daniel O. Vidal, Andrew Burnette, Jennifer Eschbacher, Beth Hermes, Ardene Noss, Rosy Singh, Matthew L. Anderson, Patricia D. Castro, Michael Ittmann, David Huntsman, Bernard Kohl, Xuan Le, Richard Thorp, Chris Andry, Elizabeth R. Duffy, Vladimir Lyadov, Oxana Paklina, Galiya Setdikova, Alexey Shabunin, Mikhail Tavobilov, Christopher McPherson, Ronald Warnick, Ross Berkowitz, Daniel Cramer, Colleen Feltmate, Neil Horowitz, Adam Kibel, Michael Muto, Chandrajit P. Raut, Andrei Malykh, Jill S. Barnholtz-Sloan, Wendi Barrett, Karen Devine, Jordonna Fulop, Quinn T. Ostrom, Kristen Shimmel, Yingli Wolinsky, Andrew E. Sloan, Agostino De Rose, Felice Giuliante, Marc Goodman, Beth Y. Karlan, Curt H. Hagedorn, John Eckman, Jodi Harr, Jerome Myers, Kelinda Tucker, Leigh Anne Zach, Brenda Deyarmin, Hai Hu, Leonid Kvecher, Caroline Larson, Richard J. Mural, Stella Somiari, Ales Vicha, Tomas Zelinka, Joseph Bennett, Mary Iacocca, Brenda Rabeno, Patricia Swanson, Mathieu Latour, Louis Lacombe, Bernard Têtu, Alain Bergeron, Mary McGraw, Susan M. Staugaitis, John Chabot, Hanina Hibshoosh, Antonia Sepulveda, Tao Su, Timothy Wang, Olga Potapova, Olga Voronina, Laurence Desjardins, Odette Mariani, Sergio Roman-Roman, Xavier Sastre, Marc-Henri Stern, Feixiong Cheng, Sabina Signoretti, Andrew Berchuck, Darell Bigner, Eric Lipp, Jeffrey Marks, Shannon McCall, Roger McLendon, Angeles Secord, Alexis Sharp, Madhusmita Behera, Daniel J. 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Metwalli, Karel Pacak, Peter A. Pinto, Mark Schiffman, Laura S. Schmidt, Cathy D. Vocke, Nicolas Wentzensen, Robert Worrell, Hannah Yang, Marc Moncrieff, Chandra Goparaju, Jonathan Melamed, Harvey Pass, Natalia Botnariuc, Irina Caraman, Mircea Cernat, Inga Chemencedji, Adrian Clipca, Serghei Doruc, Ghenadie Gorincioi, Sergiu Mura, Maria Pirtac, Irina Stancul, Diana Tcaciuc, Monique Albert, Iakovina Alexopoulou, Angel Arnaout, John Bartlett, Jay Engel, Sebastien Gilbert, Jeremy Parfitt, Harman Sekhon, George Thomas, Doris M. Rassl, Robert C. Rintoul, Carlo Bifulco, Raina Tamakawa, Walter Urba, Nicholas Hayward, Henri Timmers, Anna Antenucci, Francesco Facciolo, Gianluca Grazi, Mirella Marino, Roberta Merola, Ronald de Krijger, Anne-Paule Gimenez-Roqueplo, Alain Piché, Simone Chevalier, Ginette McKercher, Kivanc Birsoy, Gene Barnett, Cathy Brewer, Carol Farver, Theresa Naska, Nathan A. Pennell, Daniel Raymond, Cathy Schilero, Kathy Smolenski, Felicia Williams, Carl Morrison, Jeffrey A. Borgia, Michael J. Liptay, Mark Pool, Christopher W. Seder, Kerstin Junker, Larsson Omberg, Mikhail Dinkin, George Manikhas, Domenico Alvaro, Maria Consiglia Bragazzi, Vincenzo Cardinale, Guido Carpino, Eugenio Gaudio, David Chesla, Sandra Cottingham, Michael Dubina, Fedor Moiseenko, Renumathy Dhanasekaran, Karl-Friedrich Becker, Klaus-Peter Janssen, Julia Slotta-Huspenina, Mohamed H. Abdel-Rahman, Dina Aziz, Sue Bell, Colleen M. Cebulla, Amy Davis, Rebecca Duell, J. Bradley Elder, Joe Hilty, Bahavna Kumar, James Lang, Norman L. Lehman, Randy Mandt, Phuong Nguyen, Robert Pilarski, Karan Rai, Lynn Schoenfield, Kelly Senecal, Paul Wakely, Paul Hansen, Ronald Lechan, James Powers, Arthur Tischler, William E. Grizzle, Katherine C. Sexton, Alison Kastl, Joel Henderson, Sima Porten, Jens Waldmann, Martin Fassnacht, Sylvia L. Asa, Dirk Schadendorf, Marta Couce, Markus Graefen, Hartwig Huland, Guido Sauter, Thorsten Schlomm, Ronald Simon, Pierre Tennstedt, Oluwole Olabode, Mark Nelson, Oliver Bathe, Peter R. Carroll, June M. Chan, Philip Disaia, Pat Glenn, Robin K. Kelley, Charles N. Landen, Joanna Phillips, Michael Prados, Jeffry Simko, Karen Smith-McCune, Scott VandenBerg, Kevin Roggin, Ashley Fehrenbach, Ady Kendler, Suzanne Sifri, Ruth Steele, Antonio Jimeno, Francis Carey, Ian Forgie, Massimo Mannelli, Michael Carney, Brenda Hernandez, Benito Campos, Christel Herold-Mende, Christin Jungk, Andreas Unterberg, Andreas von Deimling, Aaron Bossler, Joseph Galbraith, Laura Jacobus, Michael Knudson, Tina Knutson, Deqin Ma, Mohammed Milhem, Rita Sigmund, Andrew K. Godwin, Rashna Madan, Howard G. Rosenthal, Clement Adebamowo, Sally N. Adebamowo, Alex Boussioutas, David Beer, Thomas Giordano, Anne-Marie Mes-Masson, Fred Saad, Therese Bocklage, Lisa Landrum, Robert Mannel, Kathleen Moore, Katherine Moxley, Russel Postier, Joan Walker, Rosemary Zuna, Michael Feldman, Federico Valdivieso, Rajiv Dhir, James Luketich, Edna M. Mora Pinero, Mario Quintero-Aguilo, Carlos Gilberto Carlotti, Jose Sebastião Dos Santos, Rafael Kemp, Ajith Sankarankuty, Daniela Tirapelli, James Catto, Kathy Agnew, Elizabeth Swisher, Jenette Creaney, Bruce Robinson, Carl Simon Shelley, Eryn M. Godwin, Sara Kendall, Cassaundra Shipman, Carol Bradford, Thomas Carey, Andrea Haddad, Jeffey Moyer, Lisa Peterson, Mark Prince, Laura Rozek, Gregory Wolf, Rayleen Bowman, Kwun M. Fong, Ian Yang, Robert Korst, W. Kimryn Rathmell, J. Leigh Fantacone-Campbell, Jeffrey A. Hooke, Albert J. Kovatich, Craig D. Shriver, John DiPersio, Bettina Drake, Ramaswamy Govindan, Sharon Heath, Timothy Ley, Brian Van Tine, Peter Westervelt, Mark A. Rubin, Jung Il Lee, Natália D. Aredes, Armaz Mariamidze, Wang Y., Xu X., Maglic D., Dill M.T., Mojumdar K., Ng P.K.-S., Jeong K.J., Tsang Y.H., Moreno D., Bhavana V.H., Peng X., Ge Z., Chen H., Li J., Chen Z., Zhang H., Han L., Du D., Creighton C.J., Mills G.B., Caesar-Johnson S.J., Demchok J.A., Felau I., Kasapi M., Ferguson M.L., Hutter C.M., Sofia H.J., Tarnuzzer R., Wang Z., Yang L., Zenklusen J.C., Zhang J.J., Chudamani S., Liu J., Lolla L., Naresh R., Pihl T., Sun Q., Wan Y., Wu Y., Cho J., DeFreitas T., Frazer S., Gehlenborg N., Getz G., Heiman D.I., Kim J., Lawrence M.S., Lin P., Meier S., Noble M.S., Saksena G., Voet D., Bernard B., Chambwe N., Dhankani V., Knijnenburg T., Kramer R., Leinonen K., Liu Y., Miller M., Reynolds S., Shmulevich I., Thorsson V., Zhang W., Akbani R., Broom B.M., Hegde A.M., Ju Z., Kanchi R.S., Korkut A., Liang H., Ling S., Liu W., Lu Y., Ng K.-S., Rao A., Ryan M., Wang J., Weinstein J.N., Zhang J., Abeshouse A., Armenia J., Chakravarty D., Chatila W.K., de Bruijn I., Gao J., Gross B.E., Heins Z.J., Kundra R., La K., Ladanyi M., Luna A., Nissan M.G., Ochoa A., Phillips S.M., Reznik E., Sanchez-Vega F., Sander C., Schultz N., Sheridan R., Sumer S.O., Sun Y., Taylor B.S., Anur P., Peto M., Spellman P., Benz C., Stuart J.M., Wong C.K., Yau C., Hayes D.N., Parker J.S., Wilkerson M.D., Ally A., Balasundaram M., Bowlby R., Brooks D., Carlsen R., Chuah E., Dhalla N., Holt R., Jones S.J.M., Kasaian K., Lee D., Ma Y., Marra M.A., Mayo M., Moore R.A., Mungall A.J., Mungall K., Robertson A.G., Sadeghi S., Schein J.E., Sipahimalani P., Tam A., Thiessen N., Tse K., Wong T., Berger A.C., Beroukhim R., Cherniack A.D., Cibulskis C., Gabriel S.B., Gao G.F., Ha G., Meyerson M., Schumacher S.E., Shih J., Kucherlapati M.H., Kucherlapati R.S., Baylin S., Cope L., Danilova L., Bootwalla M.S., Lai P.H., Maglinte D.T., Van Den Berg D.J., Weisenberger D.J., Auman J.T., Balu S., Bodenheimer T., Fan C., Hoadley K.A., Hoyle A.P., Jefferys S.R., Jones C.D., Meng S., Mieczkowski P.A., Mose L.E., Perou A.H., Perou C.M., Roach J., Shi Y., Simons J.V., Skelly T., Soloway M.G., Tan D., Veluvolu U., Fan H., Hinoue T., Laird P.W., Shen H., Zhou W., Bellair M., Chang K., Covington K., Dinh H., Doddapaneni H., Donehower L.A., Drummond J., Gibbs R.A., Glenn R., Hale W., Han Y., Hu J., Korchina V., Lee S., Lewis L., Li W., Liu X., Morgan M., Morton D., Muzny D., Santibanez J., Sheth M., Shinbrot E., Wang L., Wang M., Wheeler D.A., Xi L., Zhao F., Hess J., Appelbaum E.L., Bailey M., Cordes M.G., Ding L., Fronick C.C., Fulton L.A., Fulton R.S., Kandoth C., Mardis E.R., McLellan M.D., Miller C.A., Schmidt H.K., Wilson R.K., Crain D., Curley E., Gardner J., Lau K., Mallery D., Morris S., Paulauskis J., Penny R., Shelton C., Shelton T., Sherman M., Thompson E., Yena P., Bowen J., Gastier-Foster J.M., Gerken M., Leraas K.M., Lichtenberg T.M., Ramirez N.C., Wise L., Zmuda E., Corcoran N., Costello T., Hovens C., Carvalho A.L., de Carvalho A.C., Fregnani J.H., Longatto-Filho A., Reis R.M., Scapulatempo-Neto C., Silveira H.C.S., Vidal D.O., Burnette A., Eschbacher J., Hermes B., Noss A., Singh R., Anderson M.L., Castro P.D., Ittmann M., Huntsman D., Kohl B., Le X., Thorp R., Andry C., Duffy E.R., Lyadov V., Paklina O., Setdikova G., Shabunin A., Tavobilov M., McPherson C., Warnick R., Berkowitz R., Cramer D., Feltmate C., Horowitz N., Kibel A., Muto M., Raut C.P., Malykh A., Barnholtz-Sloan J.S., Barrett W., Devine K., Fulop J., Ostrom Q.T., Shimmel K., Wolinsky Y., Sloan A.E., De Rose A., Giuliante F., Goodman M., Karlan B.Y., Hagedorn C.H., Eckman J., Harr J., Myers J., Tucker K., Zach L.A., Deyarmin B., Hu H., Kvecher L., Larson C., Mural R.J., Somiari S., Vicha A., Zelinka T., Bennett J., Iacocca M., Rabeno B., Swanson P., Latour M., Lacombe L., Tetu B., Bergeron A., McGraw M., Staugaitis S.M., Chabot J., Hibshoosh H., Sepulveda A., Su T., Wang T., Potapova O., Voronina O., Desjardins L., Mariani O., Roman-Roman S., Sastre X., Stern M.-H., Cheng F., Signoretti S., Berchuck A., Bigner D., Lipp E., Marks J., McCall S., McLendon R., Secord A., Sharp A., Behera M., Brat D.J., Chen A., Delman K., Force S., Khuri F., Magliocca K., Maithel S., Olson J.J., Owonikoko T., Pickens A., Ramalingam S., Shin D.M., Sica G., Van Meir E.G., Eijckenboom W., Gillis A., Korpershoek E., Looijenga L., Oosterhuis W., Stoop H., van Kessel K.E., Zwarthoff E.C., Calatozzolo C., Cuppini L., Cuzzubbo S., DiMeco F., Finocchiaro G., Mattei L., Perin A., Pollo B., Chen C., Houck J., Lohavanichbutr P., Hartmann A., Stoehr C., Stoehr R., Taubert H., Wach S., Wullich B., Kycler W., Murawa D., Wiznerowicz M., Chung K., Edenfield W.J., Martin J., Baudin E., Bubley G., Bueno R., De Rienzo A., Richards W.G., Kalkanis S., Mikkelsen T., Noushmehr H., Scarpace L., Girard N., Aymerich M., Campo E., Gine E., Guillermo A.L., Van Bang N., Hanh P.T., Phu B.D., Tang Y., Colman H., Evason K., Dottino P.R., Martignetti J.A., Gabra H., Juhl H., Akeredolu T., Stepa S., Hoon D., Ahn K., Kang K.J., Beuschlein F., Breggia A., Birrer M., Bell D., Borad M., Bryce A.H., Castle E., Chandan V., Cheville J., Copland J.A., Farnell M., Flotte T., Giama N., Ho T., Kendrick M., Kocher J.-P., Kopp K., Moser C., Nagorney D., O'Brien D., O'Neill B.P., Patel T., Petersen G., Que F., Rivera M., Roberts L., Smallridge R., Smyrk T., Stanton M., Thompson R.H., Torbenson M., Yang J.D., Zhang L., Brimo F., Ajani J.A., Gonzalez A.M.A., Behrens C., Bondaruk J., Broaddus R., Czerniak B., Esmaeli B., Fujimoto J., Gershenwald J., Guo C., Lazar A.J., Logothetis C., Meric-Bernstam F., Moran C., Ramondetta L., Rice D., Sood A., Tamboli P., Thompson T., Troncoso P., Tsao A., Wistuba I., Carter C., Haydu L., Hersey P., Jakrot V., Kakavand H., Kefford R., Lee K., Long G., Mann G., Quinn M., Saw R., Scolyer R., Shannon K., Spillane A., Stretch J., Synott M., Thompson J., Wilmott J., Al-Ahmadie H., Chan T.A., Ghossein R., Gopalan A., Levine D.A., Reuter V., Singer S., Singh B., Tien N.V., Broudy T., Mirsaidi C., Nair P., Drwiega P., Miller J., Smith J., Zaren H., Park J.-W., Hung N.P., Kebebew E., Linehan W.M., Metwalli A.R., Pacak K., Pinto P.A., Schiffman M., Schmidt L.S., Vocke C.D., Wentzensen N., Worrell R., Yang H., Moncrieff M., Goparaju C., Melamed J., Pass H., Botnariuc N., Caraman I., Cernat M., Chemencedji I., Clipca A., Doruc S., Gorincioi G., Mura S., Pirtac M., Stancul I., Tcaciuc D., Albert M., Alexopoulou I., Arnaout A., Bartlett J., Engel J., Gilbert S., Parfitt J., Sekhon H., Thomas G., Rassl D.M., Rintoul R.C., Bifulco C., Tamakawa R., Urba W., Hayward N., Timmers H., Antenucci A., Facciolo F., Grazi G., Marino M., Merola R., de Krijger R., Gimenez-Roqueplo A.-P., Piche A., Chevalier S., McKercher G., Birsoy K., Barnett G., Brewer C., Farver C., Naska T., Pennell N.A., Raymond D., Schilero C., Smolenski K., Williams F., Morrison C., Borgia J.A., Liptay M.J., Pool M., Seder C.W., Junker K., Omberg L., Dinkin M., Manikhas G., Alvaro D., Bragazzi M.C., Cardinale V., Carpino G., Gaudio E., Chesla D., Cottingham S., Dubina M., Moiseenko F., Dhanasekaran R., Becker K.-F., Janssen K.-P., Slotta-Huspenina J., Abdel-Rahman M.H., Aziz D., Bell S., Cebulla C.M., Davis A., Duell R., Elder J.B., Hilty J., Kumar B., Lang J., Lehman N.L., Mandt R., Nguyen P., Pilarski R., Rai K., Schoenfield L., Senecal K., Wakely P., Hansen P., Lechan R., Powers J., Tischler A., Grizzle W.E., Sexton K.C., Kastl A., Henderson J., Porten S., Waldmann J., Fassnacht M., Asa S.L., Schadendorf D., Couce M., Graefen M., Huland H., Sauter G., Schlomm T., Simon R., Tennstedt P., Olabode O., Nelson M., Bathe O., Carroll P.R., Chan J.M., Disaia P., Glenn P., Kelley R.K., Landen C.N., Phillips J., Prados M., Simko J., Smith-McCune K., VandenBerg S., Roggin K., Fehrenbach A., Kendler A., Sifri S., Steele R., Jimeno A., Carey F., Forgie I., Mannelli M., Carney M., Hernandez B., Campos B., Herold-Mende C., Jungk C., Unterberg A., von Deimling A., Bossler A., Galbraith J., Jacobus L., Knudson M., Knutson T., Ma D., Milhem M., Sigmund R., Godwin A.K., Madan R., Rosenthal H.G., Adebamowo C., Adebamowo S.N., Boussioutas A., Beer D., Giordano T., Mes-Masson A.-M., Saad F., Bocklage T., Landrum L., Mannel R., Moore K., Moxley K., Postier R., Walker J., Zuna R., Feldman M., Valdivieso F., Dhir R., Luketich J., Pinero E.M.M., Quintero-Aguilo M., Carlotti C.G., Dos Santos J.S., Kemp R., Sankarankuty A., Tirapelli D., Catto J., Agnew K., Swisher E., Creaney J., Robinson B., Shelley C.S., Godwin E.M., Kendall S., Shipman C., Bradford C., Carey T., Haddad A., Moyer J., Peterson L., Prince M., Rozek L., Wolf G., Bowman R., Fong K.M., Yang I., Korst R., Rathmell W.K., Fantacone-Campbell J.L., Hooke J.A., Kovatich A.J., Shriver C.D., DiPersio J., Drake B., Govindan R., Heath S., Ley T., Van Tine B., Westervelt P., Rubin M.A., Lee J.I., Aredes N.D., Mariamidze A., Camargo F., SAIC-F-Frederick, Inc, and Leidos Biomedical Research, Inc.
Subjects: TAZ, 0301 basic medicine, pan-cancer analysis, PROMOTES, Somatic cell, Cancer Genome Atlas Research Network, Protein-Serine-Threonine Kinase, law.invention, law, Neoplasms, LS2_1, LS4_6, TUMOR PROGRESSION, pathway activity, MicroRNA, Prognosis, PANCREATIC-CANCER, 3. Good health, Gene Expression Regulation, Neoplastic, Hippo signaling, ORGAN SIZE CONTROL, GROWTH, YAP, Life Sciences & Biomedicine, pan-cancer analysi, Human, Signal Transduction, animal structures, Prognosi, Computational biology, Biology, Protein Serine-Threonine Kinases, Models, Biological, General Biochemistry, Genetics and Molecular Biology, Article, NO, 03 medical and health sciences, Cell Line, Tumor, GENES SUPRESSORES DE TUMOR, microRNA, BREAST-CANCER, Humans, Hippo Signaling Pathway, Gene, prognostic power, Hippo signaling pathway, Science & Technology, Squamous cell cancer, Base Sequence, driver mutation, Cell Biology, TCGA, GENE, MicroRNAs, 030104 developmental biology, tumor subtype, CELLS, Mutation, miRNA regulation, Neoplasm, Target signature, Suppressor
Abstract: SUMMARY Hippo signaling has been recognized as a key tumor suppressor pathway. Here, we perform a comprehensive molecular characterization of 19 Hippo core genes in 9,125 tumor samples across 33 cancer types using multidimensional “omic” data from The Cancer Genome Atlas. We identify somatic drivers among Hippo genes and the related microRNA (miRNA) regulators, and using functional genomic approaches, we experimentally characterize YAP and TAZ mutation effects and miR-590 and miR-200a regulation for TAZ. Hippo pathway activity is best characterized by a YAP/TAZ transcriptional target signature of 22 genes, which shows robust prognostic power across cancer types. Our elastic-net integrated modeling further reveals cancer-type-specific pathway regulators and associated cancer drivers. Our results highlight the importance of Hippo signaling in squamous cell cancers, characterized by frequent amplification of YAP/TAZ, high expression heterogeneity, and significant prognostic patterns. This study represents a systems-biology approach to characterizing key cancer signaling pathways in the post-genomic era., Graphical Abstract, In Brief Wang et al. perform a comprehensive analysis of 19 Hippo core genes across 33 cancer types using multidimensional “omic” data from The Cancer Genome Atlas. They characterize Hippo pathway activity by a YAP/TAZ transcriptional target signature of 22 genes and highlight the importance of Hippo signaling in squamous cell cancers.
Published: 2018

34. Distribution of Mediastinal Lesions Across Multi-Institutional, International, Radiology Databases.

Author: Roden AC, Fang W, Shen Y, Carter BW, White DB, Jenkins SM, Spears GM, Molina JR, Klang E, Segni MD, Ackman JB, Sanchez EZ, Girard N, Shumeri E, Revel MP, Chassagnon G, Rubinowitz A, Dicks D, Detterbeck F, Ko JP, Falkson CB, Sigurdson S, Segreto S, Del Vecchio S, Palmieri G, Ottaviano M, Marino M, Korst R, and Marom EM
Subjects: China, Europe, Humans, Mediastinum, Retrospective Studies, Lung Neoplasms, Mediastinal Neoplasms diagnostic imaging, Mediastinal Neoplasms epidemiology, Radiology, Thymus Neoplasms
Abstract: Introduction: Mediastinal lesions are uncommon; studies on their distribution are, in general, small and from a single institution. Furthermore, these studies are usually based on pathology or surgical databases and, therefore, miss many lesions that did not undergo biopsy or resection. Our aim was to identify the distribution of lesions in the mediastinum in a large international, multi-institutional cohort., Methods: At each participating institution, a standardized retrospective radiology database search was performed for interpretations of computed tomography, positron emission tomography-computed tomography, and magnetic resonance imaging scans including any of the following terms: "mediastinal nodule," "mediastinal lesion," "mediastinal mass," or "mediastinal abnormality" (2011-2014). Standardized data were collected. Statistical analysis was performed., Results: Among 3308 cases, thymomas (27.8%), benign mediastinal cysts (20.0%), and lymphomas (16.1%) were most common. The distribution of lesions varied among mediastinal compartments; thymomas (38.3%), benign cysts (16.8%), and neurogenic tumors (53.9%) were the most common lesions in the prevascular, visceral, and paravertebral mediastinum, respectively (p < 0.001). Mediastinal compartment was associated with age; patients with paravertebral lesions were the youngest (p < 0.0001). Mediastinal lesions differed by continent or country, with benign cysts being the most common mediastinal lesions in the People's Republic of China, thymomas in Europe, and lymphomas in North America and Israel (p < 0.001). Benign cysts, thymic carcinomas, and metastases were more often seen in larger hospitals, whereas lymphomas and thymic hyperplasia occurred more often in smaller hospitals (p < 0.01)., Conclusions: Our study confirmed that the spectrum and frequency of mediastinal lesions depend on mediastinal compartment and age. This information provides helpful demographic data and is important when considering the differential diagnosis of a mediastinal lesion., (Copyright © 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)
Published: 2020
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35. Paraneoplastic Syndromes and Thymic Malignancies: An Examination of the International Thymic Malignancy Interest Group Retrospective Database.

Author: Padda SK, Yao X, Antonicelli A, Riess JW, Shang Y, Shrager JB, Korst R, Detterbeck F, Huang J, Burt BM, Wakelee HA, and Badve SS
Subjects: Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Databases, Factual, Female, Humans, Male, Middle Aged, Paraneoplastic Syndromes pathology, Retrospective Studies, Thymus Neoplasms pathology, Young Adult, Paraneoplastic Syndromes diagnosis, Thymus Neoplasms diagnosis
Abstract: Introduction: Thymic epithelial tumors (TETs) are associated with paraneoplastic/autoimmune (PN/AI) syndromes. Myasthenia gravis is the most common PN/AI syndrome associated with TETs., Methods: The International Thymic Malignancy Interest Group retrospective database was examined to determine (1) baseline and treatment characteristics associated with PN/AI syndromes and (2) the prognostic role of PN/AI syndromes for patients with TETs. The competing risks model was used to estimate cumulative incidence of recurrence (CIR) and the Kaplan-Meier method was used to calculate overall survival (OS). A Cox proportional hazards model was used for multivariate analysis., Results: A total of 6670 patients with known PN/AI syndrome status from 1951 to 2012 were identified. PN/AI syndromes were associated with younger age, female sex, thymoma histologic type, earlier stage, and an increased rate of total thymectomy and complete resection status. There was a statistically significant lower CIR in the group with a PN/AI syndrome than in the group without a PN/AI syndrome (10-year CIR 17.3% versus 21.2%, respectively [p = 0.0003]). The OS was improved in the group with a PN/AI syndrome compared to the group without a PN/AI syndrome (median OS 21.6 years versus 17.0 years, respectively [hazard ratio = 0.63, 95% confidence interval: 0.54-0.74, p < 0.0001]). However, in the multivariate model for recurrence-free survival and OS, PN/AI syndrome was not an independent prognostic factor., Discussion: Previously, there have been mixed data regarding the prognostic role of PN/AI syndromes for patients with TETs. Here, using the largest data set in the world for TETs, PN/AI syndromes were associated with favorable features (i.e., earlier stage and complete resection status) but were not an independent prognostic factor for patients with TETs., (Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)
Published: 2018
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36. The Integrated Genomic Landscape of Thymic Epithelial Tumors.

Author: Radovich M, Pickering CR, Felau I, Ha G, Zhang H, Jo H, Hoadley KA, Anur P, Zhang J, McLellan M, Bowlby R, Matthew T, Danilova L, Hegde AM, Kim J, Leiserson MDM, Sethi G, Lu C, Ryan M, Su X, Cherniack AD, Robertson G, Akbani R, Spellman P, Weinstein JN, Hayes DN, Raphael B, Lichtenberg T, Leraas K, Zenklusen JC, Fujimoto J, Scapulatempo-Neto C, Moreira AL, Hwang D, Huang J, Marino M, Korst R, Giaccone G, Gokmen-Polar Y, Badve S, Rajan A, Ströbel P, Girard N, Tsao MS, Marx A, Tsao AS, and Loehrer PJ
Subjects: Adolescent, Adult, Aged, Aged, 80 and over, Female, Genomics, Humans, Male, Middle Aged, Young Adult, Mutation genetics, Neoplasms, Glandular and Epithelial genetics, Thymoma genetics, Thymus Neoplasms genetics, Transcription Factors, TFII genetics
Abstract: Thymic epithelial tumors (TETs) are one of the rarest adult malignancies. Among TETs, thymoma is the most predominant, characterized by a unique association with autoimmune diseases, followed by thymic carcinoma, which is less common but more clinically aggressive. Using multi-platform omics analyses on 117 TETs, we define four subtypes of these tumors defined by genomic hallmarks and an association with survival and World Health Organization histological subtype. We further demonstrate a marked prevalence of a thymoma-specific mutated oncogene, GTF2I, and explore its biological effects on multi-platform analysis. We further observe enrichment of mutations in HRAS, NRAS, and TP53. Last, we identify a molecular link between thymoma and the autoimmune disease myasthenia gravis, characterized by tumoral overexpression of muscle autoantigens, and increased aneuploidy., (Copyright © 2018 Elsevier Inc. All rights reserved.)
Published: 2018
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37. Computed Tomography Screening for Lung Cancer: Mediastinal Lymph Node Resection in Stage IA Nonsmall Cell Lung Cancer Manifesting as Subsolid and Solid Nodules.

Author: Flores RM, Nicastri D, Bauer T, Aye R, Andaz S, Kohman L, Sheppard B, Mayfield W, Thurer R, Korst R, Straznicka M, Grannis F, Pass H, Connery C, Yip R, Smith JP, Yankelevitz DF, Henschke CI, and Altorki NK
Subjects: Aged, Carcinoma, Non-Small-Cell Lung diagnostic imaging, Carcinoma, Non-Small-Cell Lung surgery, Databases, Factual, Diagnosis, Differential, Disease-Free Survival, Female, Follow-Up Studies, Humans, Lung Neoplasms diagnostic imaging, Lung Neoplasms mortality, Lung Neoplasms surgery, Male, Middle Aged, Neoplasm Invasiveness pathology, Neoplasm Staging, Pneumonectomy methods, Positron-Emission Tomography methods, Retrospective Studies, Solitary Pulmonary Nodule diagnostic imaging, Solitary Pulmonary Nodule mortality, Solitary Pulmonary Nodule surgery, Survival Rate, Treatment Outcome, Carcinoma, Non-Small-Cell Lung pathology, Early Detection of Cancer methods, Lung Neoplasms pathology, Solitary Pulmonary Nodule pathology, Tomography, X-Ray Computed methods
Abstract: Objective: To compare long-term survival rates of patients with first, primary, clinical stage IA nonsmall cell lung cancer from a large cohort undergoing computed tomography screening with and without mediastinal lymph node resection (MLNR) under an Institutional Review Board-approved common protocol from 1992 to 2014., Background: Assessing survival differences of patients with and without MLNR manifesting as solid and subsolid nodules., Methods: Long-term Kaplan-Meier (K-M) survival rates for those with and without MLNR were compared and Cox regression analyses were used to adjust for demographic, computed tomography, and surgical covariates., Results: The long-term K-M rates for 462 with and 145 without MLNR was 92% versus 96% (P = 0.19), respectively. For 203 patients with a subsolid nodule, 151 with and 52 without MLNR, the rate was 100%. For the 404 patients with a solid nodule, 311 with and 93 without MLNR, the rate was 87% versus 94% (P = 0.24) and Cox regression showed no statistically significant difference (P = 0.28) when adjusted for all covariates. Risk of dying increased significantly with increasing decades of age (hazard ratio [HR] 2.3, 95% confidence interval [CI] 1.4-3.8), centrally located tumor (HR 2.5, 95% CI 1.2-5.2), tumor size 21 to 30 mm (HR 2.7, 95% CI 1.2-6.0), and invasion beyond the lung stroma (HR 3.0, 95% CI 1.4-6.1). For the 346 patients with MLNR, tumor size was 20 mm or less; K-M rates for the 269 patients with and 169 patients without MLNR were also not significantly different (HR 2.1, P = 0.24)., Conclusions: It is not mandatory to perform MLNR when screen-diagnosed nonsmall cell lung cancer manifests as a subsolid nodule.
Published: 2017
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38. Thymic Carcinoma Management Patterns among International Thymic Malignancy Interest Group (ITMIG) Physicians with Consensus from the Thymic Carcinoma Working Group.

Author: Shepherd A, Riely G, Detterbeck F, Simone CB 2nd, Ahmad U, Huang J, Korst R, Rajan A, and Rimner A
Subjects: Consensus, Disease Management, Humans, Physicians, Prognosis, Thymoma diagnosis, Thymus Neoplasms diagnosis, Practice Patterns, Physicians', Thymoma therapy, Thymus Neoplasms therapy
Abstract: Introduction: Thymic carcinomas are rare epithelial malignancies with limited data to guide management., Methods: To identify areas of agreement and variability in current clinical practice, a 16-question electronic survey was given to members of the International Thymic Malignancy Interest Group (ITMIG). Areas of controversy were discussed with the Thymic Carcinoma Working Group and consensus was achieved, as described., Results: A total of 100 ITMIG members responded. There was general agreement regarding the role for multimodality therapy with definitive surgical resection in physically fit patients with advanced but resectable disease. Areas of controversy included the need for histologic confirmation before surgery, the role of adjuvant therapy, the optimal first-line chemotherapy regimen, and the recommended treatment course for marginally resectable disease with invasion into the great vessels, pericardium, and lungs., Conclusions: The results of the questionnaire provide a description of the management of thymic carcinoma by 100 ITMIG members with a specific interest or expertise in thymic malignancies. Although there was agreement in some areas, clinical practice appears to vary significantly. There is a great need for collaborative research to identify optimal evaluation and treatment strategies. Given the need for multimodality therapy in many cases, a multidisciplinary discussion of the management of patients with thymic carcinoma is critical., (Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)
Published: 2017
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39. Comparison of outcomes between neuroendocrine thymic tumours and other subtypes of thymic carcinomas: a joint analysis of the European Society of Thoracic Surgeons and the International Thymic Malignancy Interest Group.

Author: Filosso PL, Yao X, Ruffini E, Ahmad U, Antonicelli A, Huang J, Guerrera F, Venuta F, van Raemdonck D, Travis W, Lucchi M, Rimner A, Thomas P, Weder W, Rocco G, Detterbeck F, and Korst R
Subjects: Adolescent, Adult, Aged, Aged, 80 and over, Child, Databases, Factual, Disease-Free Survival, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Neoplasms, Glandular and Epithelial classification, Neoplasms, Glandular and Epithelial mortality, Neoplasms, Glandular and Epithelial surgery, Neuroendocrine Tumors classification, Neuroendocrine Tumors surgery, Proportional Hazards Models, Retrospective Studies, Survival Analysis, Thymoma classification, Thymoma surgery, Thymus Neoplasms classification, Thymus Neoplasms surgery, Young Adult, Neuroendocrine Tumors mortality, Thymoma mortality, Thymus Neoplasms mortality
Abstract: Objectives: The latest World Health Organization (WHO) histological classification divides thymic epithelial tumours in thymomas and thymic carcinomas (TCs), the latter also including the neuroendocrine thymic tumours (NETTs). NETTs and other TC histotypes have been described to have a significantly lower survival than thymomas, but these two groups of tumours have rarely been compared directly. Using the European Society of Thoracic Surgeons and the International Thymic Malignancy Interest Group datasets, we wanted to study this issue., Methods: This is a retrospective multicentre cohort study of patients operated for TC. Outcome measures were overall survival (OS) and recurrence-free survival (RFS). OS was analysed using the Kaplan-Meier method and RFS was assessed using competing risk analysis. The association with clinical and prognostic factors for OS and RFS was evaluated with log-rank test and Gray's test, respectively., Results: A total of 1247 tumours (1042 TCs) were collected between 1984 and 2012. A R0 resection was performed in 363 TCs and in 52 NETTs. The median follow-up was 4.4 years for TCs and 4.1 years for NETTs. Owing to the missing values for survival information, a total of 728 TC patients and 132 NETTs were included in the OS analysis. Among them, 262 TC and 39 NETT patients died. The median OS was 6.6 years for TC and 7.5 years for NETTs. The overall 5-year survival rates were 60% for TC and 68% for NETTs; 10-year survival rates were 40% for TCs and 39% for NETTs (P = 0.19). Five-year RFS was 0.35 and 0.34 for TCs and NETTs (P = 0.36). On multivariate analysis, histology did not influence either OS (P = 0.79) or RFS (P = 0.59)., Conclusions: This represents the largest clinical series of TCs and NETTs collected. Despite the biological aggressiveness of these rare neoplasms, the 5-year survival rate after resection is over 60% and TCs and NETT showed a similar rate of survival and recurrences after surgery., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)
Published: 2016
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40. Robotic gastrectomy and esophagogastrectomy: A single center experience of 105 cases.

Author: Harrison LE, Yiengpruksawan A, Patel J, Itskovich A, Lee B, and Korst R
Subjects: Adult, Aged, Aged, 80 and over, Carcinoma pathology, Feasibility Studies, Female, Humans, Learning Curve, Length of Stay, Male, Middle Aged, Operative Time, Retrospective Studies, Stomach Neoplasms pathology, Treatment Outcome, Carcinoma surgery, Esophagectomy statistics & numerical data, Gastrectomy statistics & numerical data, Robotic Surgical Procedures statistics & numerical data, Stomach Neoplasms surgery
Abstract: Background: A robotic approach to general surgery procedures may provide improved postoperative outcomes compared to either open or laparoscopic approaches. The role of robotics for gastroesophageal surgery, however, is still being evaluated., Study Design: A review of the prospective database for robotic surgery at Valley Hospital between January 2002 and March 2014 identified 105 patients who underwent robotic gastric and esophageal resection. Patient demographics and perioperative factors were studied., Results: Over a 12 years period, 105 patients underwent robotic gastroesophageal resection. The median operative time for distal gastrectomy (230 min [112-327]) was significantly less compared to either total gastrectomy (302 min [214-364]) or esophagogastrectomy (309 min [190-682]). The length of stay for patients undergoing distal gastrectomy (6 days [4-32]) was also significantly less than patients undergoing total gastrectomy (11 days [7-43]), as well as esophagogastrectomy (9 days [5-64]). In regard to the learning curve to perform robotic gastroesophageal surgery, there was a significant correlation between operative time and overall experience., Conclusions: This study demonstrated that robotic gastroesophageal surgery is feasible and can be safely performed. Assuming familiarity with the open procedures and acquisition of basic robotic skills, the learning curve for robotic gastroesophageal surgery requires approximately 20 cases., (© 2015 Wiley Periodicals, Inc.)
Published: 2015
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41. The International Thymic Malignancy Interest Group thymic initiative: a state-of-the-art study of thymic malignancies.

Author: Detterbeck F and Korst R
Subjects: Community-Institutional Relations, Consensus, Forecasting, Humans, Practice Guidelines as Topic, Practice Patterns, Physicians' standards, Biomedical Research organization & administration, Biomedical Research standards, Biomedical Research trends, Cooperative Behavior, Evidence-Based Medicine organization & administration, Evidence-Based Medicine standards, Evidence-Based Medicine trends, International Agencies organization & administration, International Agencies standards, International Agencies trends, International Cooperation, Medical Oncology organization & administration, Medical Oncology standards, Medical Oncology trends, Thymus Neoplasms diagnosis, Thymus Neoplasms epidemiology, Thymus Neoplasms therapy
Abstract: Thymic malignancies are relatively rare tumors. A general lack of knowledge, misconceptions about benignancy, confusion about the definition of terms, and variability in reporting of outcomes have further hampered progress in these diseases. The International Thymic Malignancy Interest Group has emerged to counter these challenges and has brought together a worldwide multidisciplinary community determined to improve outcomes for these patients. Although the organization is young (initiated in 2010), major early accomplishments have created a foundation and infrastructure for scientific research. These include consensus definitions of terms, an unprecedented global database, development of practical clinical resources and, together with the International Association for the Study of Lung Cancer, development of proposals for the first formal stage classification of these malignant tumors. Many articles have been published or are under way, and a second phase of projects building on the early success is proceeding. The greatest accomplishment of the International Thymic Malignancy Interest Group lies in the establishment of an open culture of collaboration and the engagement of a broad group of individuals united by a common mission. It is a testament to what can be achieved, despite ongoing and inherent challenges, by determination and a collective effort., (Copyright © 2014 Elsevier Inc. All rights reserved.)
Published: 2014
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42. Balancing curability and unnecessary surgery in the context of computed tomography screening for lung cancer.

Author: Flores R, Bauer T, Aye R, Andaz S, Kohman L, Sheppard B, Mayfield W, Thurer R, Smith M, Korst R, Straznicka M, Grannis F, Pass H, Connery C, Yip R, Smith JP, Yankelevitz D, Henschke C, and Altorki N
Subjects: Aged, Early Detection of Cancer, Early Medical Intervention, Female, Humans, Kaplan-Meier Estimate, Lung Neoplasms mortality, Male, Middle Aged, Neoplasm Staging, Predictive Value of Tests, Prognosis, Time Factors, United States, Lung Neoplasms diagnostic imaging, Lung Neoplasms surgery, Mass Screening methods, Patient Selection, Pneumonectomy methods, Thoracic Surgery, Video-Assisted, Tomography, X-Ray Computed, Unnecessary Procedures
Abstract: Objective: Surgical management is a critical component of computed tomography (CT) screening for lung cancer. We report the results for US sites in a large ongoing screening program, the International Early Lung Cancer Action Program (I-ELCAP)., Methods: We identified all patients who underwent surgical resection. We compared the results before (1993-2005) and after (2006-2011) termination of the National Lung Screening Trial to identify emerging trends., Results: Among 31,646 baseline and 37,861 annual repeat CT screenings, 492 patients underwent surgical resection; 437 (89%) were diagnosed with lung cancer; 396 (91%) had clinical stage I disease. In the 54 (11%) patients with nonmalignant disease, resection was sublobar in 48 and lobectomy in 6. The estimated cure rate based on the 15-year Kaplan-Meier survival for all 428 patients (excluding 9 typical carcinoids) with lung cancer was 84% (95% confidence interval [CI], 80%-88%) and 88% (95% CI, 83%-92%) for clinical stage I disease resected within 1 month of diagnosis. Video-assisted thoracoscopic surgery and sublobar resection increased significantly, from 10% to 34% (P < .0001) and 22% to 34% (P = .01) respectively; there were no significant differences in the percentage of malignant diagnoses (90% vs 87%, P = .36), clinical stage I (92% vs 89%, P = .33), pathologic stage I (85% vs 82%, P = .44), tumor size (P = .61), or cell type (P = .81)., Conclusions: The frequency and extent of surgery for nonmalignant disease can be minimized in a CT screening program and provide a high cure rate for those diagnosed with lung cancer and undergoing surgical resection., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)
Published: 2014
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43. Sublobar resection is equivalent to lobectomy for clinical stage 1A lung cancer in solid nodules.

Author: Altorki NK, Yip R, Hanaoka T, Bauer T, Aye R, Kohman L, Sheppard B, Thurer R, Andaz S, Smith M, Mayfield W, Grannis F, Korst R, Pass H, Straznicka M, Flores R, and Henschke CI
Subjects: Adult, Aged, Carcinoma, Non-Small-Cell Lung diagnostic imaging, Carcinoma, Non-Small-Cell Lung pathology, Early Detection of Cancer, Female, Humans, Kaplan-Meier Estimate, Logistic Models, Lung Neoplasms diagnostic imaging, Lung Neoplasms pathology, Male, Middle Aged, Multivariate Analysis, Neoplasm Staging, Pneumonectomy adverse effects, Predictive Value of Tests, Propensity Score, Proportional Hazards Models, Risk Factors, Time Factors, Tomography, X-Ray Computed, Treatment Outcome, Tumor Burden, Carcinoma, Non-Small-Cell Lung surgery, Lung Neoplasms surgery, Pneumonectomy methods
Abstract: Objectives: A single randomized trial established lobectomy as the standard of care for the surgical treatment of early-stage non-small cell lung cancer. Recent advances in imaging/staging modalities and detection of smaller tumors have once again rekindled interest in sublobar resection for early-stage disease. The objective of this study was to compare lung cancer survival in patients with non-small cell lung cancer with a diameter of 30 mm or less with clinical stage 1 disease who underwent lobectomy or sublobar resection., Methods: We identified 347 patients diagnosed with lung cancer who underwent lobectomy (n = 294) or sublobar resection (n = 53) for non-small cell lung cancer manifesting as a solid nodule in the International Early Lung Cancer Action Program from 1993 to 2011. Differences in the distribution of the presurgical covariates between sublobar resection and lobectomy were assessed using unadjusted P values determined by logistic regression analysis. Propensity scoring was performed using the same covariates. Differences in the distribution of the same covariates between sublobar resection and lobectomy were assessed using adjusted P values determined by logistic regression analysis with adjustment for the propensity scores. Lung cancer-specific survival was determined by the Kaplan-Meier method. Cox survival regression analysis was used to compare sublobar resection with lobectomy, adjusted for the propensity scores, surgical, and pathology findings, when adjusted and stratified by propensity quintiles., Results: Among 347 patients, 10-year Kaplan-Meier for 53 patients treated by sublobar resection compared with 294 patients treated by lobectomy was 85% (95% confidence interval, 80-91) versus 86% (confidence interval, 75-96) (P = .86). Cox survival analysis showed no significant difference between sublobar resection and lobectomy when adjusted for propensity scores or when using propensity quintiles (P = .62 and P = .79, respectively). For those with cancers 20 mm or less in diameter, the 10-year rates were 88% (95% confidence interval, 82-93) versus 84% (95% confidence interval, 73-96) (P = .45), and Cox survival analysis showed no significant difference between sublobar resection and lobectomy using either approach (P = .42 and P = .52, respectively)., Conclusions: Sublobar resection and lobectomy have equivalent survival for patients with clinical stage IA non-small cell lung cancer in the context of computed tomography screening for lung cancer., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)
Published: 2014
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44. A phase II trial of preoperative combined-modality therapy for localized esophageal carcinoma: initial results.

Author: Bains MS, Stojadinovic A, Minsky B, Rusch V, Turnbull A, Korst R, Ginsberg R, Kelsen DP, and Ilson DH
Subjects: Adenocarcinoma diagnosis, Adenocarcinoma drug therapy, Adenocarcinoma radiotherapy, Adenocarcinoma surgery, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Squamous Cell diagnosis, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell radiotherapy, Carcinoma, Squamous Cell surgery, Cisplatin administration & dosage, Combined Modality Therapy, Diagnostic Imaging, Esophageal Neoplasms diagnosis, Esophageal Neoplasms drug therapy, Esophageal Neoplasms radiotherapy, Esophageal Neoplasms surgery, Female, Humans, Male, Middle Aged, Paclitaxel administration & dosage, Treatment Outcome, Adenocarcinoma therapy, Carcinoma, Squamous Cell therapy, Esophageal Neoplasms therapy
Abstract: Objective: We sought to evaluate treatment response to a novel combined-modality treatment regimen for localized esophageal carcinoma., Methods: Localized esophageal carcinoma was confirmed with endoscopic ultrasonography, computed tomography, and positron emission tomography before induction therapy. This therapy consisted of combined cisplatin/paclitaxel (cisplatin, 75 mg/m(2); paclitaxel, 175 mg/m(2); 2 cycles, 3-hour infusion) for weeks 1 and 4, combined cisplatin (30 mg. m(-2). wk(-1)) and paclitaxel (30-80 mg. m(-2). wk(-1), 96-hour infusion) with concurrent radiation (external beam, 1.8 Gy/d; total, 50.4 Gy) for weeks 7 to 12, and esophagectomy for week 16 after restaging confirmed resectability., Results: Forty-one patients (36 men) with adenocarcinoma (n = 25) or squamous cell carcinoma (n = 16) were enrolled. Thirty-six patients completed treatment, of whom 34 (85%) had locally advanced disease of clinical stage T3-4 N0-1. Symptoms resolved or improved in 35 (92%) of 38 patients after induction chemotherapy. Fourteen (35%) and 10 (24%) patients experienced grade III/IV myelosuppression during induction chemotherapy and chemoradiation, respectively. Two (5%) had grade III and none had grade IV esophagitis during chemoradiation. Only 2 (5%) patients required enteral feeding-tube support during therapy. Of 33 R0 resections, 9 (26%) had complete pathologic disease, and 4 (12%) had microscopic residual disease. Major (eg, anastomotic response, delayed stricture, and respiratory failure) postoperative morbidity occurred in 13 (36%) of 36 patients. Operative mortality was 5.5% (2/36)., Conclusion: This regimen of induction concurrent chemoradiation followed by surgical intervention for esophageal carcinoma produces rapid dysphagia relief with initial chemotherapy, has a high overall response rate, and has acceptable toxicity levels.
Published: 2002
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45. An initial experience with FDG-PET in the imaging of residual disease after induction therapy for lung cancer.

Author: Akhurst T, Downey RJ, Ginsberg MS, Gonen M, Bains M, Korst R, Ginsberg RJ, Rusch VW, and Larson SM
Subjects: Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung pathology, Carcinoma, Non-Small-Cell Lung radiotherapy, Fluorodeoxyglucose F18, Humans, Image Interpretation, Computer-Assisted, Lung Neoplasms drug therapy, Lung Neoplasms pathology, Lung Neoplasms radiotherapy, Neoplasm Staging, Neoplasm, Residual, Radiopharmaceuticals, Retrospective Studies, Carcinoma, Non-Small-Cell Lung diagnostic imaging, Lung Neoplasms diagnostic imaging, Tomography, Emission-Computed
Abstract: Background: The 2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) imaging is an advance over computed tomography alone in the staging of untreated nonsmall cell lung cancer (NSCLC). Aside from one 9-patient study, there are no data comparing FDG-PET imaging with surgical staging of NSCLC after induction therapy., Methods: We reviewed our institutional experience with FDG-PET imaging followed by surgical staging of nonsmall cell lung cancer after induction therapy. A nuclear physician blinded to surgical findings reviewed the FDG-PET scans and assigned a clinical TNM stage. A thoracic surgeon assigned a pathologic TNM stage. Then the clinical TNM stage and the pathologic TNM stage were compared., Results: Fifty-six patients (30 males and 26 females; median, age 60) with nonsmall cell lung cancer underwent chemotherapy (40 patients), chemoradiation (11 patients), or radiation alone (5 patients) followed by PET and operations. PET had a positive predictive value of 98% for detecting residual viable disease in the primary tumor. PET over-staged nodal status in 33% of patients, under staged nodal status in 15%, and was correct in 52%. PET correctly classified all patients with M1 disease., Conclusions: Positron emission tomography after induction therapy accurately detects residual viable primary tumor, but not the involvement of mediastinal lymph nodes.
Published: 2002
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46. Intratumoral administration of low doses of an adenovirus vector encoding tumor necrosis factor alpha together with naive dendritic cells elicits significant suppression of tumor growth without toxicity.

Author: Kianmanesh A, Hackett NR, Lee JM, Kikuchi T, Korst RJ, and Crystal RG
Subjects: Animals, Cell Division, Cell Survival, Dendritic Cells transplantation, Female, Genetic Therapy methods, Immunotherapy, Adoptive methods, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Microscopy, Fluorescence, Neoplasm Transplantation, Neoplasms genetics, Neoplasms pathology, T-Lymphocytes, Cytotoxic immunology, Time Factors, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha administration & dosage, Tumor Necrosis Factor-alpha genetics, Adenoviridae genetics, Dendritic Cells immunology, Genetic Vectors administration & dosage, Neoplasms immunology, Neoplasms therapy, Tumor Necrosis Factor-alpha adverse effects, Tumor Necrosis Factor-alpha therapeutic use
Abstract: Although tumor necrosis factor alpha (TNF-alpha) is a potent cytokine with a myriad of innate immune antitumor properties, systemic administration of TNF-alpha is associated with significant toxicity, limiting the use of the TNF-alpha protein as an antitumor therapeutic. On the basis of the knowledge that dendritic cells (DCs) play a central role in initiating antitumor adaptive immune responses, we hypothesized that intratumoral administration of low doses of an adenovirus encoding TNF-alpha (AdTNF-alpha) together with syngeneic DCs would act synergistically to suppress preexisting tumors. As a model, four different tumor cell lines, all resistant in vitro to the TNF-alpha protein, were implanted in syngeneic mice, and established tumors received intratumor AdTNF-alpha alone or in combination with DCs. At high doses (10(9) PFU), AdTNF-alpha alone suppressed tumor growth, but was associated with systemic toxicity. A 100-fold lower AdTNF-alpha concentration (10(7) PFU) or high doses of the control vector AdNull had no systemic toxicity, but also minimal suppression of tumor growth. In contrast, local administration of the low dose (10(7) PFU) of AdTNF-alpha in combination with syngeneic DCs (AdTNF-alpha + DCs) elicited marked tumor suppression without toxicity. Administration of AdTNF-alpha + DCs into tumors elicited tumor-specific cytotoxic T cells and protected animals against subsequent challenge with the same tumor, suggesting that AdTNF-alpha + DC therapy induced tumor-specific adaptive immune host responses. Consistent with this concept, studies with syngeneic knockout mice showed that MHC class I molecules on DCs as well as CD8(+) T cells were necessary for the antitumor effect of intratumor AdTNF-alpha + DCs. These data demonstrate that the combination of intratumoral administration of the TNF-alpha cDNA together with naive DCs can evoke tumor suppression without systemic toxicity, providing a new paradigm for the use of TNF-alpha as antitumor therapy.
Published: 2001
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47. Morbidity and mortality after neoadjuvant therapy for lung cancer: the risks of right pneumonectomy.

Author: Martin J, Ginsberg RJ, Abolhoda A, Bains MS, Downey RJ, Korst RJ, Weigel TL, Kris MG, Venkatraman ES, and Rusch VW
Subjects: Adult, Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung mortality, Carcinoma, Non-Small-Cell Lung pathology, Combined Modality Therapy, Female, Hospital Mortality, Humans, Lung Neoplasms mortality, Lung Neoplasms pathology, Male, Middle Aged, Neoplasm Staging, Risk, Survival Analysis, Carcinoma, Non-Small-Cell Lung surgery, Lung Neoplasms surgery, Neoadjuvant Therapy adverse effects, Pneumonectomy adverse effects, Postoperative Complications mortality
Abstract: Background: The risks of complications in patients undergoing thoracotomy after neoadjuvant therapy for nonsmall cell lung cancer remain controversial. We reviewed our experience to define it further., Methods: All patients undergoing thoracotomy after induction chemotherapy from 1993 through 1999 were reviewed. Univariate and multivariate methods for logistic regression model were used to identify predictors of adverse events., Results: Induction chemotherapy included mitomycin, vinblastine, and cisplatin (179 patients), carboplatin and paclitaxel (152 patients), and other combinations (139 patients). Eighty-five patients (18%) received preoperative radiation. Operations were pneumonectomy (97 patients), lobectomy (297 patients), lesser resection (18 patients), and exploration only (58 patients). Total mortality was 7 of 297 (2.4%) and 11 of 97 (11.3%) for all lobectomies and pneumonectomies, respectively, but mortality was 11 of 46 (23.9%) for right pneumonectomy. Complications developed in 179 patients (38%). By multiple regression analysis, right pneumonectomy (p = 0.02), blood loss (p = 0.01), and forced expiratory volume in one second (percent predicted) (p = 0.01) predicted complications. No factor emerged to explain this high right pneumonectomy mortality rate., Conclusions: Pulmonary resection after neoadjuvant therapy is associated with acceptable overall morbidity and mortality. However, right pneumonectomy is associated with a significantly increased risk and should be performed only in selected patients.
Published: 2001
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48. Adenovirus gene transfer vectors inhibit growth of lymphatic tumor metastases independent of a therapeutic transgene.

Author: Korst RJ, Ailawadi M, Lee JM, Lee S, Yamada R, Mahtabifard A, and Crystal RG
Subjects: Adenoviridae genetics, Adenoviridae immunology, Animals, Cell Division, Flow Cytometry, Genetic Therapy, Genetic Vectors genetics, Genetic Vectors immunology, Killer Cells, Natural immunology, Lymph Nodes immunology, Lymph Nodes pathology, Lymphatic Metastasis genetics, Male, Mice, Mice, Inbred C3H, Sequence Deletion, Time Factors, Tumor Cells, Cultured, Adenoviridae physiology, Genetic Vectors administration & dosage, Interferon-gamma immunology, Lymphatic Metastasis immunology, Lymphatic Metastasis pathology, Transgenes genetics
Abstract: Adenovirus (Ad) gene transfer vectors traffic to regional lymph nodes (RLNs) after footpad injections in mice, resulting in localized production of interferon gamma (IFN-gamma). With this background, we evaluated the hypothesis that Ad vector administration may inhibit RLN tumor metastasis independent of the transgene in the expression cassette. Tumors of MM48, a cell line with a propensity toward lymphogenous metastasis, were established in the footpads of syngeneic C3H mice, and E1(-)E3(-) Ad vectors encoding no transgene (AdNull) or encoding an irrelevant transgene (AdCD; Escherichia coli cytosine deaminase with no 5-fluorocytosine administration) were administered (10(10) particles) in a peritumoral location. Both vectors suppressed the growth of tumor in the regional (popliteal) lymph node. This effect was localized to the regional, but not distant, lymph nodes (p < 0.05). Heat inactivation of the vector or decreasing the dose of the vector to 10(9) particles did not suppress RLN growth of the tumor when compared with 10(10) particles of active AdNull (p < 0.05 and p < 0.01, respectively). The ability of an E1(-)E4(-) vector expressing beta-galactosidase (AdRSVbetagal.11) to suppress RLN tumor growth showed that the E4 region of the Ad vector was not responsible for the effect. Blocking either IFN-gamma or natural killer (NK) cells with systemic antibody treatment in immunocompetent mice allowed rapid growth of RLN metastases despite Ad vector administration, and Ad vector injection into the footpads of tumor-free mice induced the accumulation of NK cells in the RLN. These data demonstrate that, in a metastatic murine tumor model, a low dose (10(10) particles) of replication-deficient Ad vectors inhibits RLN metastases independent of a therapeutic transgene, an effect that is mediated, at least in part, by IFN-gamma and NK cells.
Published: 2001
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49. Appropriate surgical treatment of resectable non-small-cell lung cancer.

Author: Korst RJ and Ginsberg RJ
Subjects: Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Non-Small-Cell Lung mortality, Chemotherapy, Adjuvant, Humans, Lung Neoplasms mortality, Lymph Node Excision, Neoplasm Staging, Radiotherapy, Adjuvant, Thoracic Surgery, Video-Assisted, Carcinoma, Non-Small-Cell Lung surgery, Lung Neoplasms surgery, Pneumonectomy
Abstract: Patients with early-stage non-small-cell lung cancer (NSCLC) should be treated with complete surgical resection whenever possible. Incomplete resections do not cure, and the optimal pulmonary resection is anatomic lobectomy. Limited resections (wedge resection and segmentectomy) are associated with a threefold increase in local recurrence, which translates into decreased survival. The addition of mediastinal lymph node dissection produces the best pathologic staging but has never been shown to improve survival. Resections can be performed through a variety of incisions and even using minimally invasive techniques, but posterolateral thoracotomy seems to provide the best exposure and is used most frequently. Adjuvant radiotherapy in both the preoperative and postoperative settings does not improve survival in patients with resected NSCLC. Similarly, postoperative chemotherapy cannot be advocated in these patients based on the current data. Improved survival has been demonstrated in the randomized setting for patients with locally advanced, resectable disease (N2) using preoperative (induction) chemo(radio)therapy, but the numbers are small. Patients with this stage of NSCLC should be enrolled in induction therapy protocols whenever possible to confirm the efficacy of this approach.
Published: 2001
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50. Effects of diltiazem prophylaxis on the incidence and clinical outcome of atrial arrhythmias after thoracic surgery.

Author: Amar D, Roistacher N, Rusch VW, Leung DH, Ginsburg I, Zhang H, Bains MS, Downey RJ, Korst RJ, and Ginsberg RJ
Subjects: Administration, Oral, Aged, Atrial Fibrillation epidemiology, Atrial Flutter epidemiology, Double-Blind Method, Female, Hospital Costs, Humans, Incidence, Injections, Intravenous, Male, Middle Aged, Postoperative Complications epidemiology, Pulmonary Surgical Procedures, Tachycardia, Supraventricular epidemiology, Treatment Outcome, Atrial Fibrillation prevention & control, Atrial Flutter prevention & control, Calcium Channel Blockers therapeutic use, Diltiazem therapeutic use, Postoperative Complications prevention & control, Tachycardia, Supraventricular prevention & control
Abstract: Objectives: We sought to determine whether early prophylaxis with an L -type calcium channel blocker reduces the incidence and morbidity associated with atrial fibrillation/flutter and supraventricular tachyarrhythmia after major thoracic operations., Methods: In this randomized, double-blind, placebo-controlled study, 330 patients were given either intravenous diltiazem (n = 167) or placebo (n = 163) immediately after lobectomy (> or =60 years) or pneumonectomy (> or =18 years) and orally thereafter for 14 days. The primary end point with respect to efficacy was a sustained (> or =15 minutes) or clinically significant atrial arrhythmia during treatment., Results: Postoperative atrial arrhythmias (atrial fibrillation/flutter = 60; supraventricular tachyarrhythmias = 5) occurred in 25 (15%) of the 167 patients in the diltiazem group and 40 (25%) of the 163 patients in the placebo group (P = .03). When compared with placebo, diltiazem nearly halved the incidence of clinically significant arrhythmias (17/167 [10%] vs. 31/163 [19%], P = .02). The 2 groups did not differ in the incidence of other major postoperative complications or overall duration or costs of hospitalization. No serious adverse effects caused by diltiazem were seen., Conclusions: After major thoracic operations, prophylactic diltiazem reduced the incidence of clinically significant atrial arrhythmias in patients considered at high risk for this complication.
Published: 2000
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