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5. 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

6. 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. 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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., 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

8. Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin

Author

Hoadley, K., Yau, C., Wolf, D., Cherniack, A., Tamborero, D., Ng, S., Leiserson, M., Niu, B., McLellan, M., Uzunangelov, V., Zhang, J., Kandoth, C., Akbani, R., Shen, H., Omberg, L., Chu, A., Margolin, A., van't Veer, L., Lopez-Bigas, N., Laird, P., Raphael, B., Ding, L., Robertson, A., Byers, L., Mills, G., Weinstein, J., Van Waes, C., Chen, Z., Collisson, E., Benz, C., Perou, C., Stuart, J., Abbott, R., Abbott, S., Aksoy, B., Aldape, K., Ally, A., Amin, S., Anastassiou, D., Auman, J., Baggerly, K., Balasundaram, M., Balu, S., Baylin, S., Benz, S., Berman, B., Bernard, B., Bhatt, A., Birol, I., Black, A., Bodenheimer, T., Bootwalla, M., Bowen, J., Bressler, R., Bristow, C., Brooks, A., Broom, B., Buda, E., Burton, R., Butterfield, Y., Carlin, D., Carter, S., Casasent, T., Chang, K., Chanock, S., Chin, L., Cho, D., Cho, J., Chuah, E., Chun, H., Cibulskis, K., Ciriello, G., Cleland, J., Cline, M., Craft, B., Creighton, C., Danilova, L., Davidsen, T., Davis, C., Dees, N., Delehaunty, K., Demchok, J., Dhalla, N., DiCara, D., Dinh, H., Dobson, J., Dodda, D., Doddapaneni, H., Donehower, L., Dooling, D., Dresdner, G., Drummond, J., Eakin, A., Edgerton, M., Eldred, J., Eley, G., Ellrott, K., Fan, C., Fei, S., Felau, I., Frazer, S., Freeman, S., Frick, J., Fronick, C., Fulton, L., Fulton, R., Gabriel, S., Gao, J., Gastier-Foster, J., Gehlenborg, N., George, M., Getz, G., Gibbs, R., Goldman, M., Gonzalez-Perez, A., Gross, B., Guin, R., Gunaratne, P., Hadjipanayis, A., Hamilton, M., Hamilton, S., Han, L., Han, Y., Harper, H., Haseley, P., Haussler, D., Hayes, D., Heiman, D., Helman, E., Helsel, C., Herbrich, S., Herman, J., Hinoue, T., Hirst, C., Hirst, M., Holt, R., Hoyle, A., Iype, L., Jacobsen, A., Jeffreys, S., Jensen, M., Jones, C., Jones, S., Ju, Z., Jung, J., Kahles, A., Kahn, A., Kalicki-Veizer, J., Kalra, D., Kanchi, K., Kane, D., Kim, H., Kim, J., Knijnenburg, T., Koboldt, D., Kovar, C., Kramer, R., Kreisberg, R., Kucherlapati, R., Ladanyi, M., Lander, E., Larson, D., Lawrence, M., Lee, D., Lee, E., Lee, S., Lee, W., Lehmann, K., Leinonen, K., Leraas, K., Lerner, S., Levine, D., Lewis, L., Ley, T., Li, H., Li, J., Li, W., Liang, H., Lichtenberg, T., Lin, J., Lin, L., Lin, P., Liu, W., Liu, Y., Lorenzi, P., Lu, C., Lu, Y., Luquette, L., Ma, S., Magrini, V., Mahadeshwar, H., Mardis, E., Marra, M., Mayo, M., McAllister, C., McGuire, S., McMichael, J., Melott, J., Meng, S., Meyerson, M., Mieczkowski, P., Miller, C., Miller, M., Moore, R., Morgan, M., Morton, D., Mose, L., Mungall, A., Muzny, D., Nguyen, L., Noble, M., Noushmehr, H., O'Laughlin, M., Ojesina, A., Yang, T., Ozenberger, B., Pantazi, A., Parfenov, M., Park, P., Parker, J., Paull, E., Pedamallu, C., Pihl, T., Pohl, C., Pot, D., Protopopov, A., Przytycka, T., Radenbaugh, A., Ramirez, N., Ramirez, R., Ratsch, G., Reid, J., Ren, X., Reva, B., Reynolds, S., Rhie, S., Roach, J., Rovira, H., Ryan, M., Saksena, G., Salama, S., Sander, C., Santoso, N., Schein, J., Schmidt, H., Schultz, N., Schumacher, S., Seidman, J., Senbabaoglu, Y., Seth, S., Sharpe, S., Shen, R., Sheth, M., Shi, Y., Shmulevich, I., Silva, G., Simons, J., Sinha, R., Sipahimalani, P., Smith, S., Sofia, H., Sokolov, A., Soloway, M., Song, X., Sougnez, C., Spellman, P., Staudt, L., Stewart, C., Stojanov, P., Su, X., Sumer, S., Sun, Y., Swatloski, T., Tabak, B., Tam, A., Tan, D., Tang, J., Tarnuzzer, R., Taylor, B., Thiessen, N., Thorsson, V., Triche, T., Van Den Berg, D., Vandin, F., Varhol, Richard, Vaske, C., Veluvolu, U., Verhaak, R., Voet, D., Walker, J., Wallis, J., Waltman, P., Wan, Y., Wang, M., Wang, W., Wang, Z., Waring, S., Weinhold, N., Weisenberger, D., Wendl, M., Wheeler, D., Wilkerson, M., Wilson, R., Wise, L., Wong, A., Wu, C., Wu, H., Wu, J., Wylie, T., Xi, L., Xi, R., Xia, Z., Xu, A., Yang, D., Yang, L., Yang, Y., Yao, J., Yao, R., Ye, K., Yoshihara, K., Yuan, Y., Yung, A., Zack, T., Zeng, D., Zenklusen, J., Zhang, H., Zhang, N., Zhang, Q., Zhang, W., Zhao, W., Zheng, S., Zhu, J., Zmuda, E., Zou, L., Hoadley, K., Yau, C., Wolf, D., Cherniack, A., Tamborero, D., Ng, S., Leiserson, M., Niu, B., McLellan, M., Uzunangelov, V., Zhang, J., Kandoth, C., Akbani, R., Shen, H., Omberg, L., Chu, A., Margolin, A., van't Veer, L., Lopez-Bigas, N., Laird, P., Raphael, B., Ding, L., Robertson, A., Byers, L., Mills, G., Weinstein, J., Van Waes, C., Chen, Z., Collisson, E., Benz, C., Perou, C., Stuart, J., Abbott, R., Abbott, S., Aksoy, B., Aldape, K., Ally, A., Amin, S., Anastassiou, D., Auman, J., Baggerly, K., Balasundaram, M., Balu, S., Baylin, S., Benz, S., Berman, B., Bernard, B., Bhatt, A., Birol, I., Black, A., Bodenheimer, T., Bootwalla, M., Bowen, J., Bressler, R., Bristow, C., Brooks, A., Broom, B., Buda, E., Burton, R., Butterfield, Y., Carlin, D., Carter, S., Casasent, T., Chang, K., Chanock, S., Chin, L., Cho, D., Cho, J., Chuah, E., Chun, H., Cibulskis, K., Ciriello, G., Cleland, J., Cline, M., Craft, B., Creighton, C., Danilova, L., Davidsen, T., Davis, C., Dees, N., Delehaunty, K., Demchok, J., Dhalla, N., DiCara, D., Dinh, H., Dobson, J., Dodda, D., Doddapaneni, H., Donehower, L., Dooling, D., Dresdner, G., Drummond, J., Eakin, A., Edgerton, M., Eldred, J., Eley, G., Ellrott, K., Fan, C., Fei, S., Felau, I., Frazer, S., Freeman, S., Frick, J., Fronick, C., Fulton, L., Fulton, R., Gabriel, S., Gao, J., Gastier-Foster, J., Gehlenborg, N., George, M., Getz, G., Gibbs, R., Goldman, M., Gonzalez-Perez, A., Gross, B., Guin, R., Gunaratne, P., Hadjipanayis, A., Hamilton, M., Hamilton, S., Han, L., Han, Y., Harper, H., Haseley, P., Haussler, D., Hayes, D., Heiman, D., Helman, E., Helsel, C., Herbrich, S., Herman, J., Hinoue, T., Hirst, C., Hirst, M., Holt, R., Hoyle, A., Iype, L., Jacobsen, A., Jeffreys, S., Jensen, M., Jones, C., Jones, S., Ju, Z., Jung, J., Kahles, A., Kahn, A., Kalicki-Veizer, J., Kalra, D., Kanchi, K., Kane, D., Kim, H., Kim, J., Knijnenburg, T., Koboldt, D., Kovar, C., Kramer, R., Kreisberg, R., Kucherlapati, R., Ladanyi, M., Lander, E., Larson, D., Lawrence, M., Lee, D., Lee, E., Lee, S., Lee, W., Lehmann, K., Leinonen, K., Leraas, K., Lerner, S., Levine, D., Lewis, L., Ley, T., Li, H., Li, J., Li, W., Liang, H., Lichtenberg, T., Lin, J., Lin, L., Lin, P., Liu, W., Liu, Y., Lorenzi, P., Lu, C., Lu, Y., Luquette, L., Ma, S., Magrini, V., Mahadeshwar, H., Mardis, E., Marra, M., Mayo, M., McAllister, C., McGuire, S., McMichael, J., Melott, J., Meng, S., Meyerson, M., Mieczkowski, P., Miller, C., Miller, M., Moore, R., Morgan, M., Morton, D., Mose, L., Mungall, A., Muzny, D., Nguyen, L., Noble, M., Noushmehr, H., O'Laughlin, M., Ojesina, A., Yang, T., Ozenberger, B., Pantazi, A., Parfenov, M., Park, P., Parker, J., Paull, E., Pedamallu, C., Pihl, T., Pohl, C., Pot, D., Protopopov, A., Przytycka, T., Radenbaugh, A., Ramirez, N., Ramirez, R., Ratsch, G., Reid, J., Ren, X., Reva, B., Reynolds, S., Rhie, S., Roach, J., Rovira, H., Ryan, M., Saksena, G., Salama, S., Sander, C., Santoso, N., Schein, J., Schmidt, H., Schultz, N., Schumacher, S., Seidman, J., Senbabaoglu, Y., Seth, S., Sharpe, S., Shen, R., Sheth, M., Shi, Y., Shmulevich, I., Silva, G., Simons, J., Sinha, R., Sipahimalani, P., Smith, S., Sofia, H., Sokolov, A., Soloway, M., Song, X., Sougnez, C., Spellman, P., Staudt, L., Stewart, C., Stojanov, P., Su, X., Sumer, S., Sun, Y., Swatloski, T., Tabak, B., Tam, A., Tan, D., Tang, J., Tarnuzzer, R., Taylor, B., Thiessen, N., Thorsson, V., Triche, T., Van Den Berg, D., Vandin, F., Varhol, Richard, Vaske, C., Veluvolu, U., Verhaak, R., Voet, D., Walker, J., Wallis, J., Waltman, P., Wan, Y., Wang, M., Wang, W., Wang, Z., Waring, S., Weinhold, N., Weisenberger, D., Wendl, M., Wheeler, D., Wilkerson, M., Wilson, R., Wise, L., Wong, A., Wu, C., Wu, H., Wu, J., Wylie, T., Xi, L., Xi, R., Xia, Z., Xu, A., Yang, D., Yang, L., Yang, Y., Yao, J., Yao, R., Ye, K., Yoshihara, K., Yuan, Y., Yung, A., Zack, T., Zeng, D., Zenklusen, J., Zhang, H., Zhang, N., Zhang, Q., Zhang, W., Zhao, W., Zheng, S., Zhu, J., Zmuda, E., and Zou, L.

Abstract

© 2014 Elsevier Inc. Recent genomic analyses of pathologically defined tumor types identify 'within-a-tissue' disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-oforigin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head and neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pancancer subtypes. The multiplatform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All data sets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies.

Published
2014

9. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia

Author

Ley, T., Miller, C., Ding, L., Raphael, B., Mungall, A., Robertson, G., Hoadley, K., Triche, T., Laird, P., Baty, J., Fulton, L., Fulton, R., Heath, S., Kalicki-Veizer, J., Kandoth, C., Klco, J., Koboldt, D., Kanchi, K., Kulkarni, S., Lamprecht, T., Larson, D., Lin, G., Lu, C., McLellan, M., McMichael, J., Payton, J., Schmidt, H., Spencer, D., Tomasson, M., Wallis, J., Wartman, L., Watson, M., Welch, J., Wendl, M., Ally, A., Balasundaram, M., Birol, I., Butterfield, Y., Chiu, R., Chu, A., Chuah, E., Chun, H., Corbett, R., Dhalla, N., Guin, R., He, A., Hirst, C., Hirst, M., Holt, R., Jones, S., Karsan, A., Lee, D., Li, H., Marra, M., Mayo, M., Moore, R., Mungall, K., Parker, J., Pleasance, E., Plettner, P., Schein, J., Stoll, D., Swanson, L., Tam, A., Thiessen, N., Varhol, Richard, Wye, N., Zhao, Y., Gabriel, S., Getz, G., Sougnez, C., Zou, L., Leiserson, M., Vandin, F., Wu, H., Applebaum, F., Baylin, S., Akbani, R., Broom, B., Chen, K., Motter, T., Nguyen, K., Weinstein, J., Zhang, N., Ferguson, M., Adams, C., Black, A., Bowen, J., Gastier-Foster, J., Grossman, T., Lichtenberg, T., Wise, L., Davidsen, T., Demchok, J., Mills Shaw, K., Sheth, M., Sofia, H., Yang, L., Downing, J., Eley, G., Ley, T., Miller, C., Ding, L., Raphael, B., Mungall, A., Robertson, G., Hoadley, K., Triche, T., Laird, P., Baty, J., Fulton, L., Fulton, R., Heath, S., Kalicki-Veizer, J., Kandoth, C., Klco, J., Koboldt, D., Kanchi, K., Kulkarni, S., Lamprecht, T., Larson, D., Lin, G., Lu, C., McLellan, M., McMichael, J., Payton, J., Schmidt, H., Spencer, D., Tomasson, M., Wallis, J., Wartman, L., Watson, M., Welch, J., Wendl, M., Ally, A., Balasundaram, M., Birol, I., Butterfield, Y., Chiu, R., Chu, A., Chuah, E., Chun, H., Corbett, R., Dhalla, N., Guin, R., He, A., Hirst, C., Hirst, M., Holt, R., Jones, S., Karsan, A., Lee, D., Li, H., Marra, M., Mayo, M., Moore, R., Mungall, K., Parker, J., Pleasance, E., Plettner, P., Schein, J., Stoll, D., Swanson, L., Tam, A., Thiessen, N., Varhol, Richard, Wye, N., Zhao, Y., Gabriel, S., Getz, G., Sougnez, C., Zou, L., Leiserson, M., Vandin, F., Wu, H., Applebaum, F., Baylin, S., Akbani, R., Broom, B., Chen, K., Motter, T., Nguyen, K., Weinstein, J., Zhang, N., Ferguson, M., Adams, C., Black, A., Bowen, J., Gastier-Foster, J., Grossman, T., Lichtenberg, T., Wise, L., Davidsen, T., Demchok, J., Mills Shaw, K., Sheth, M., Sofia, H., Yang, L., Downing, J., and Eley, G.

Abstract

BACKGROUND: Many mutations that contribute to the pathogenesis of acute myeloid leukemia (AML) are undefined. The relationships between patterns of mutations and epigenetic phenotypes are not yet clear. METHODS: We analyzed the genomes of 200 clinically annotated adult cases of de novo AML, using either whole-genome sequencing (50 cases) or whole-exome sequencing (150 cases), along with RNA and microRNA sequencing and DNA-methylation analysis. RESULTS: AML genomes have fewer mutations than most other adult cancers, with an average of only 13 mutations found in genes. Of these, an average of 5 are in genes that are recurrently mutated in AML. A total of 23 genes were significantly mutated, and another 237 were mutated in two or more samples. Nearly all samples had at least 1 nonsynonymous mutation in one of nine categories of genes that are almost certainly relevant for pathogenesis, including transcription-factor fusions (18% of cases), the gene encoding nucleophosmin (NPM1) (27%), tumor-suppressor genes (16%), DNA-methylation-related genes (44%), signaling genes (59%), chromatin-modifying genes (30%), myeloid transcription-factor genes (22%), cohesin-complex genes (13%), and spliceosome-complex genes (14%). Patterns of cooperation and mutual exclusivity suggested strong biologic relationships among several of the genes and categories. CONCLUSIONS: We identified at least one potential driver mutation in nearly all AML samples and found that a complex interplay of genetic events contributes to AML pathogenesis in individual patients. The databases from this study are widely available to serve as a foundation for further investigations of AML pathogenesis, classification, and risk stratification. (Funded by the National Institutes of Health.) Copyright © 2013 Massachusetts Medical Society.

Published
2013

14. Telescoping languages : A strategy for automatic generation of scientific problem-solving systems from annotated libraries

Author

Kennedy, K., Broom, B., Cooper, K., Dongarra, J., Fowler, R., Gannon, D., Johnsson, Lennart, Mellor-Crummey, J., Torczon, L., Kennedy, K., Broom, B., Cooper, K., Dongarra, J., Fowler, R., Gannon, D., Johnsson, Lennart, Mellor-Crummey, J., and Torczon, L.

Abstract

As machines and programs have become more complex., the process of programming applications that can exploit the power of high-performance systems has become more difficult and correspondingly more labor-intensive. This has substantially widened the software gap the discrepancy between the need for new software and the aggregate capacity of the workforce to produce it. This problem has been compounded by the slow growth of programming productivity, especially for high-performance programs, over the past two decades. One way to bridge this gap is to make it possible for end users to develop programs in high-level domain-specific programming systems. In the past, a major impediment to the acceptance of such systems has been the poor performance of the resulting applications. To address this problem, we are developing a new compiler-based infrastructure, called TeleGen, that will make it practical to construct efficient domain-specific high-level languages from annotated component libraries. We call these languages telescoping languages, because they can be nested within one another. For programs written in telescoping languages. high performance and reasonable compilation times can be achieved by exhaustively analyzing the component libraries in advance to produce a language processor that recognizes and optimizes library operations as primitives in the language. The key to making this strategy practical is to keep compile times low by generating a custom compiler with extensive built-in knowledge of the underlying libraries. The goal is to achieve compile times that tire linearly proportional to the size of the program presented by the user. rather than to the aggregate size of that program plus the base libraries., QC 20100525

Published
2001
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19. Somatic metaphor: a clinical phenomenon pointing to a new model of disease, personhood, and physical reality.

Author

Broom B

Abstract

The rarely discussed phenomenon of somatic metaphor is apparent when a physical disease--in its pathology, the organ(s) involved, and/or its body location--appears to be 'saying' the same thing, expressing the same meaning, as the patient's subjective 'story,' conveyed in verbal language or in the pattern of important and meaningful events in the life of the patient. The author offers evidence that when patients presenting for diagnosis and treatment of physical disease are appraised from both normative physicalist and psychotherapy perspectives, somatic metaphors are frequently observed. Building on clinical examples, the crucial role of the clinician in observing (or failing to observe) this conjunction of physical disease and personal meaning is analyzed; a visual modeling of clinician patterns of observation is provided to facilitate clinicians in moving away from simplistic, reductionistic, observer patterns so that they may accommodate physical and 'story' perspectives in the same clinical space; biomedical and biopsychosocial models are analyzed, demonstrating that neither can explain somatic metaphors and that an alternative theory is therefore needed; and a unitary model of personhood and disease is proposed that avoids mind-body dichotomies and dualistic assumptions and lays a groundwork for the exploration of physical and subjective aspects of patient reality as playing active roles in the development and perpetuation of, and recovery from, any physical disease. [ABSTRACT FROM AUTHOR]

Published
2002

20. Intracellular immunoglobulin production in vitro by lymphocytes from patients with hypogammaglobulinaemia and their effect on normal lymphocytes.

Author

Broom, B. C., De La Concha, E. G., Webster, A. D. B., Janossy, G. J., and Asherson, G. L.

Subjects
*LYMPHOCYTES, *B cells, *IMMUNOGLOBULINS, *MITOGENS, *MITOSIS, *PATIENTS
Abstract

The ability of peripheral blood lymphocytes from twenty-two patients with late onset (acquired or common variable) hypogammaglobulinaemia to produce immunoglobulin was assessed by the immunotfuorescent detection of intracytoplasmic immunoglobulin (Ic-Ig) in cultures stimulated with pokeweed mitogen (PWM). Intracellular immunoglobulin was found in 4.9-26% of cultured cells from eighteen out of nineteen controls. In contrast nineteen out of twenty-two patients with hypo- gammaglobulinaemia showed values less than 1% and in ten no Ic-Ig was detected. Two of the remaining three patients showed normal values. Lymphocytes from eleven patients showing less than 1% positive cells were selected for mixture experiments. Lymphocytes from five of the eleven patients strongly depressed immunoglobulin synthesis by normal lymphocytes when mixed together in the presence of PWM. However, lymphocytes from these individual patients did not depress immunoglobulin production in all normal controls. [ABSTRACT FROM AUTHOR]

Published
1976

21. Rat Tumour Allografts Evoke Anaphylactic Antibody Responses.

Author

Broom, B. C. and Alexander, P.

Subjects
*IMMUNE response, *HOMOGRAFTS, *HISTAMINE, *MAST cell immunology, *TUMOR immunology, *RATS
Abstract

In vitro assays of release of histamine from peritoneal mast cells showed that Wistar rats produced anaphylactic antibody in response to a single immunization with an allogeneic sarcoma. The response occurs early after immunization, and no adjuvant is needed. The thermolability of the anaphylactic antibody suggests that it is IgE. [ABSTRACT FROM AUTHOR]

Published
1975

23. SARCOIDOSIS: CORRELATION OF DELAYED HYPERSENSITIVITY, MLC REACTIVITY AND LYMPHOCYTOTOXICITY WITH DISEASE ACTIVITY.

Author

Broom, B. C. and Maclaurin, B. P.

Subjects
*ALLERGIES, *LYMPHOPROLIFERATIVE disorders, *ANTIGENS, *MYCOBACTERIUM tuberculosis, *TUBERCULIN, *LEUCOCYTES
Abstract

Delayed skin reactivity to a battery of antigens was assessed for a series of sarcoidosis patients and closely matched controls. It was compared with the proliferative and cytotoxic capacity of corresponding blood lymphocyte preparations after challenge in mixed lymphocyte culture with an allogeneic lymphoma cell line. Skin anergy to all antigens tested was found only within the patient group having definitely active disease. These patients also showed depression of lymphocyte proliferative response in the in vitro test system as compared to matched controls and to patients with apparently inactive disease. Both of these differences were statistically significant. Skin reactivity to tuberculin was significantly depressed for the whole sarcoidosis group (both active and inactive) as compared to the control group and significant impairment of capacity to develop cytotoxicity in vitro was also found in comparison of these same groups. The results obtained confirm the association of impaired delayed skin hypersensitivity in sarcoidosis with diminished lymphocyte reactivity in vitro, especially when the disease is active. The reduced cytotoxic capacity of sarcoid lymphocytes in vitro may reflect a comparable in vivo impairment and partly explain the depressed skin tests and also contribute to the protracted nature of the disease because of failure to eradicate the postulated `sarcoid agent'. [ABSTRACT FROM AUTHOR]

Published
1973

24. Advanced optimization strategies in the Rice dHPF compiler

Author

Mellor-Crummey, J., Adve, V., Broom, B., Chavarría-Miranda, D., Fowler, R., Jin, G., Kennedy, K., and Yi, Q.

Abstract

High-Performance Fortran (HPF) was envisioned as a vehicle for modernizing legacy Fortran codes to achieve scalable parallel performance. To a large extent, today's commercially available HPF compilers have failed to deliver scalable parallel performance for a broad spectrum of applications because of insufficiently powerful compiler analysis and optimization. Substantial restructuring and hand-optimization can be required to achieve acceptable performance with an HPF port of an existing Fortran application, even for regular data-parallel applications. A key goal of the Rice dHPF compiler project has been to develop optimization techniques that enable a wide range of existing scientific applications to be ported easily to efficient HPF with minimal restructuring. This paper describes the challenges to effective parallelization presented by complex (but regular) data-parallel applications, and then describes how the novel analysis and optimization technologies in the dHPF compiler address these challenges effectively, without major rewriting of the applications. We illustrate the techniques by describing their use for parallelizing the NAS SP and BT benchmarks. The dHPF compiler generates multipartitioned parallelizations of these codes that are approaching the scalability and efficiency of sophisticated hand-coded parallelizations. Copyright © 2002 John Wiley & Sons, Ltd.

Published
2002
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25. Regulation of human cytotoxic lymphocyte responses. II. Suppression by a soluble factor produced by primed lymphocytes

Author

Crosier, P S and Broom, B C

Subjects
Cytotoxicity, Immunologic, Immunosuppression Therapy, Lymphokines, Time Factors, Dose-Response Relationship, Immunologic, Suppressor Factors, Immunologic, Humans, hemic and immune systems, chemical and pharmacologic phenomena, Lymphocytes, Lymphocyte Culture Test, Mixed, T-Lymphocytes, Regulatory, Research Article
Abstract

A soluble supernatant factor is elaborated from in vitro primed human allogeneic lymphocytes which suppresses the development of alloreactive cytotoxic lymphocytes (CTL). In contrast, supernatants obtained from primary mixed lymphocyte cultures (MLC) and primed autologous cultures were unable to suppress CTL activation, indicating that antigen restimulation was required to elicit the factor. The suppressor factor (SF) functioned in a dose-dependent manner. When the SF was added 24 or 48 hr after MLC initiation it was ineffective. However, adding the SF at culture initiation significantly reduced CTL activity, suggesting that suppression occurs either during antigen recognition or early in the CTL differentiation pathway. The SF did not function by altering the kinetics of the CTL response. Preincubation experiments showed that the SF operates by partially inactivating both MLC responder and stimulator cell populations.

Published
1981

26. Rat tumour allografts evoke anaphylactic antibody responses

Author

Broom, B C and Alexander, P

Subjects
Male, Hot Temperature, Antibodies, Neoplasm, Fibrosarcoma, biochemical phenomena, metabolism, and nutrition, Immunoglobulin E, In Vitro Techniques, Histamine Release, Bordetella pertussis, Rats, Adjuvants, Immunologic, Antibody Formation, Animals, Ascitic Fluid, Transplantation, Homologous, Immunization, Mast Cells, Sarcoma, Experimental, Anaphylaxis, Neoplasm Transplantation, Research Article, Histamine
Abstract

In vitro assays of release of histamine from peritoneal mast cells showed that Wistar rats produced anaphylactic antibody in response to a single immunization with an allogeneic sarcoma. The response occurs early after immunization, and no adjuvant is needed. The thermolability of the anaphylactic antibody suggests that it is IgE.

Published
1975

27. Youth Homelessness: The Relationships among Mental Health, Hope, and Service Satisfaction

Author

Jean Hughes, Clark, S. E., Wood, W., Cakmak, S., Cox, A., Macinnis, M., Warren, B., Handrahan, E., and Broom, B.

Subjects
Research Article
Abstract

This paper reports a mental health assessment of 60 homeless youth. Our study explored the mental health needs of youth accessing an overnight youth shelter (maximum stay 8 weeks).Participants completed an interview (45 to 120 minutes in duration) using one demographic form and one of two standardized questionnaires (Youth Self Report, Adult Self Report). Questions assessed youth mental health symptoms, examined various contacts that youth made with mainstream society (services, family), and identified potential motivating factors (hope, service satisfaction) that may play a role in fostering street survival during adolescence.Forty-eight percent of the youth were clinically symptomatic and most youth accessed a range of general health services.However, those most in need had significantly less service satisfaction, less hope about the future, and had not accessed mental health services.

28. Unique roles complementary

Author

Arra, A., Broom, B. F., Marsha Campbell-Yeo, Carson, G., Chisholm, J., Cooper, E., Forgeron, P., Macconnell, G., Morrison, D., O Neill, N., Salyzyn, D., and Widger, K.

35. Gene expression meta-analysis supports existence of molecular apocrine breast cancer with a role for androgen receptor and implies interactions with ErbB family

Author

Cristini Vittorio, Broom Bradley M, Sanga Sandeep, and Edgerton Mary E

Subjects
Internal medicine, RC31-1245, Genetics, QH426-470
Abstract

Abstract Background Pathway discovery from gene expression data can provide important insight into the relationship between signaling networks and cancer biology. Oncogenic signaling pathways are commonly inferred by comparison with signatures derived from cell lines. We use the Molecular Apocrine subtype of breast cancer to demonstrate our ability to infer pathways directly from patients' gene expression data with pattern analysis algorithms. Methods We combine data from two studies that propose the existence of the Molecular Apocrine phenotype. We use quantile normalization and XPN to minimize institutional bias in the data. We use hierarchical clustering, principal components analysis, and comparison of gene signatures derived from Significance Analysis of Microarrays to establish the existence of the Molecular Apocrine subtype and the equivalence of its molecular phenotype across both institutions. Statistical significance was computed using the Fasano & Franceschini test for separation of principal components and the hypergeometric probability formula for significance of overlap in gene signatures. We perform pathway analysis using LeFEminer and Backward Chaining Rule Induction to identify a signaling network that differentiates the subset. We identify a larger cohort of samples in the public domain, and use Gene Shaving and Robust Bayesian Network Analysis to detect pathways that interact with the defining signal. Results We demonstrate that the two separately introduced ER- breast cancer subsets represent the same tumor type, called Molecular Apocrine breast cancer. LeFEminer and Backward Chaining Rule Induction support a role for AR signaling as a pathway that differentiates this subset from others. Gene Shaving and Robust Bayesian Network Analysis detect interactions between the AR pathway, EGFR trafficking signals, and ErbB2. Conclusion We propose criteria for meta-analysis that are able to demonstrate statistical significance in establishing molecular equivalence of subsets across institutions. Data mining strategies used here provide an alternative method to comparison with cell lines for discovering seminal pathways and interactions between signaling networks. Analysis of Molecular Apocrine breast cancer implies that therapies targeting AR might be hampered if interactions with ErbB family members are not addressed.

Published
2009
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36. Youth Homelessness: The Relationships among Mental Health, Hope, and Service Satisfaction.

Author

Hughes JR, Clark SE, Wood W, Cakmak S, Cox A, Macinnis M, Warren B, Handrahan E, and Broom B

Abstract

INTRODUCTION: This paper reports a mental health assessment of 60 homeless youth. Our study explored the mental health needs of youth accessing an overnight youth shelter (maximum stay 8 weeks). METHODS: Participants completed an interview (45 to 120 minutes in duration) using one demographic form and one of two standardized questionnaires (Youth Self Report, Adult Self Report). Questions assessed youth mental health symptoms, examined various contacts that youth made with mainstream society (services, family), and identified potential motivating factors (hope, service satisfaction) that may play a role in fostering street survival during adolescence. RESULTS: Forty-eight percent of the youth were clinically symptomatic and most youth accessed a range of general health services. CONCLUSION: However, those most in need had significantly less service satisfaction, less hope about the future, and had not accessed mental health services. [ABSTRACT FROM AUTHOR]

Published
2010

37. A phase II trial of apalutamide for intermediate-risk prostate cancer and molecular correlates.

Author

Hahn AW, Manyam GC, Chapin BF, Zhang M, Yu Y, Pettaway CA, Chery L, Pisters LL, Ward JF, Gregg JR, Papadopoulos J, Kamat AM, Lozano M, Hoang A, Broom B, Wang X, Huff CD, Logothetis CJ, Troncoso P, Pilié PG, and Davis JW

Subjects
Humans, Male, Middle Aged, Aged, Thiohydantoins therapeutic use, Prostatic Neoplasms pathology, Prostatic Neoplasms drug therapy, Prostatectomy
Abstract

Objectives: To determine whether 6 months of preoperative apalutamide for intermediate-risk prostate cancer (IRPCa) reduces the aggregate postoperative radiotherapy risk and to evaluate associations of molecular perturbations with clinical outcomes in this study cohort., Patients and Methods: Between May 2018 and February 2020, eligible patients with IRPCa (Gleason 3 + 4 or 4 + 3 and clinical T2b-c or prostate-specific antigen level of 10-20 ng/mL) were treated with apalutamide 240 mg/day for 6 months followed by radical prostatectomy (RP) in this single-arm, phase II trial. The primary endpoint was presence of any adverse pathological feature at risk of pelvic radiation (pathological T stage after neoadjuvant therapy [yp]T3 or ypN1 or positive surgical margins). Translational studies, including germline and somatic DNA alterations and RNA and protein expression, were performed on post-apalutamide RP specimens, and assessed for associations with clinical outcomes., Results: A total of 40 patients underwent a RP, and only one patient discontinued apalutamide prior to 6 months. In all, 40% had adverse pathological features at time of RP, and the 3-year biochemical recurrence (BCR) rate was 15%, with 27.5% being not evaluable. Genomic alterations frequently seen in metastatic PCas, such as androgen receptor (AR), tumour protein p53 (TP53), phosphatase and tensin homologue (PTEN), or BReast CAncer associated gene (BRCA1/2) were underrepresented in this localised cohort. Adverse pathological features and BCR at 3-years were associated with increased expression of select cell cycle (e.g., E2F targets: adjusted P value [P adj ] < 0.001, normalised enrichment score [NES] 2.47) and oxidative phosphorylation (P adj  < 0.001, NES 1.62) pathways., Conclusions: Preoperative apalutamide did not reduce the aggregate postoperative radiation risk to the pre-specified threshold in unselected men with IRPCa. However, transcriptomic analysis identified key dysregulated pathways in tumours associated with adverse pathological outcomes and BCR, which warrant future study. Further investigation of preoperative therapy is underway for men with high-risk PCa., (© 2024 BJU International.)

Published
2024
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39. Optimizing the diagnosis and management of ductal prostate cancer.

Author

Ranasinghe W, Shapiro DD, Zhang M, Bathala T, Navone N, Thompson TC, Broom B, Aparicio A, Tu SM, Tang C, Davis JW, Pisters L, and Chapin BF

Subjects
Humans, Male, Carcinoma, Ductal diagnosis, Carcinoma, Ductal therapy, Prostatic Neoplasms diagnosis, Prostatic Neoplasms therapy
Abstract

Ductal adenocarcinoma (DAC) is the most common variant histological subtype of prostate carcinoma and has an aggressive clinical course. DAC is usually characterized and treated as high-risk prostatic acinar adenocarcinoma (PAC). However, DAC has a different biology to that of acinar disease, which often poses a challenge for both diagnosis and management. DAC can be difficult to identify using conventional diagnostic modalities such as serum PSA levels and multiparametric MRI, and the optimal management for localized DAC is unknown owing to the rarity of the disease. Following definitive therapy for localized disease with radical prostatectomy or radiotherapy, the majority of DACs recur with visceral metastases at low PSA levels. Various systemic therapies that have been shown to be effective in high-risk PAC have limited use in treating DAC. Although current understanding of the biology of DAC is limited, genomic analyses have provided insights into the pathology behind its aggressive behaviour and potential future therapeutic targets.

Published
2021
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40. TCF21 Promotes Luminal-Like Differentiation and Suppresses Metastasis in Bladder Cancer.

Author

Mokkapati S, Porten SP, Narayan VM, Lim AH, Jayaratna IS, Roth B, Cheng T, Navai N, Wszolek M, Melquist J, Manyam G, Choi W, Broom B, Pretzsch S, Czerniak B, McConkey DJ, and Dinney CPN

Subjects
Animals, Apoptosis, Basic Helix-Loop-Helix Transcription Factors genetics, Biomarkers, Tumor genetics, Cell Proliferation, Female, Gene Expression Profiling, Humans, Lymphatic Metastasis, Male, Mice, Mice, Nude, Middle Aged, Neoplasm Invasiveness, Prognosis, Survival Rate, Tumor Cells, Cultured, Urinary Bladder Neoplasms genetics, Urinary Bladder Neoplasms metabolism, Urinary Bladder Neoplasms pathology, Xenograft Model Antitumor Assays, Basic Helix-Loop-Helix Transcription Factors metabolism, Biomarkers, Tumor metabolism, Cell Differentiation, Gene Expression Regulation, Neoplastic, Urinary Bladder Neoplasms prevention & control
Abstract

Little is known regarding the subclone evolution process in advanced bladder cancer, particularly with respect to the genomic alterations that lead to the development of metastatic lesions. In this project, we identify gene expression signatures associated with metastatic bladder cancer through mRNA expression profiling of RNA isolated from 33 primary bladder cancer and corresponding lymph node (LN) metastasis samples. Gene expression profiling (GEP) was performed on RNA isolated using the Illumina DASL platform. We identified the developmental transcription factor TCF21 as being significantly higher in primary bladder cancer compared with LN metastasis samples. To elucidate its function in bladder cancer, loss- and gain-of-function experiments were conducted in bladder cancer cell lines with high and low expression of TCF21, respectively. We also performed GEP in bladder cancer cell lines following TCF21 overexpression. We identified 2,390 genes differentially expressed in primary bladder cancer and corresponding LN metastasis pairs at an FDR cutoff of 0.1 and a fold change of 1. Among those significantly altered, expression of TCF21 was higher in the primary tumor compared with LN metastasis. We validated this finding with qPCR and IHC on patient samples. Moreover, TCF21 expression was higher in luminal cell lines and knockdown of TCF21 increased invasion, tumor cell dissemination, and metastasis. In contrast, overexpression of TCF21 in highly metastatic basal bladder cancer cell lines decreased their invasive and metastatic potential. IMPLICATIONS: TCF21 is differentially overexpressed in primary bladder cancer compared with matched LN metastasis, with in vitro and in vivo studies demonstrating a metastasis suppressor function of this transcription factor., (©2020 American Association for Cancer Research.)

Published
2020
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41. PARP Inhibition Suppresses GR-MYCN-CDK5-RB1-E2F1 Signaling and Neuroendocrine Differentiation in Castration-Resistant Prostate Cancer.

Author

Liu B, Li L, Yang G, Geng C, Luo Y, Wu W, Manyam GC, Korentzelos D, Park S, Tang Z, Wu C, Dong Z, Sigouros M, Sboner A, Beltran H, Chen Y, Corn PG, Tetzlaff MT, Troncoso P, Broom B, and Thompson TC

Subjects
Animals, Benzamides, Bridged Bicyclo Compounds, Heterocyclic administration & dosage, Cell Line, Tumor, Cyclic N-Oxides, Cyclin-Dependent Kinase 5 genetics, Cyclin-Dependent Kinase 5 metabolism, E2F1 Transcription Factor genetics, E2F1 Transcription Factor metabolism, Gene Expression Regulation, Neoplastic drug effects, Humans, Indolizines, Male, Mice, Nude, N-Myc Proto-Oncogene Protein genetics, N-Myc Proto-Oncogene Protein metabolism, Neuroendocrine Tumors genetics, Neuroendocrine Tumors metabolism, Nitriles, Phenylthiohydantoin administration & dosage, Phenylthiohydantoin analogs & derivatives, Phthalazines administration & dosage, Piperazines administration & dosage, Prostatic Neoplasms, Castration-Resistant genetics, Prostatic Neoplasms, Castration-Resistant metabolism, Proteins metabolism, Pyridinium Compounds administration & dosage, Receptors, Glucocorticoid genetics, Receptors, Glucocorticoid metabolism, Retinoblastoma Binding Proteins genetics, Retinoblastoma Binding Proteins metabolism, Signal Transduction drug effects, Signal Transduction genetics, Treatment Outcome, Ubiquitin-Protein Ligases genetics, Ubiquitin-Protein Ligases metabolism, Xenograft Model Antitumor Assays methods, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Neuroendocrine Tumors drug therapy, Poly(ADP-ribose) Polymerase Inhibitors therapeutic use, Prostatic Neoplasms, Castration-Resistant drug therapy, Proteins genetics
Abstract

Purpose: In this study, we addressed the underlying mechanisms for the association between enzalutamide (ENZ) treatment and neuroendocrine prostate cancer (NEPC), and the critical involvement of MYCN, and loss of RB1 function in neuroendocrine differentiation (NED) of prostatic epithelial cells, and the development of NEPC. We further sought to determine whether PARP inhibition could suppress NEPC, and to identify molecular determinants of this therapeutic activity., Experimental Design: We used a novel prostate cancer patient-derived xenograft (PDX) treatment model, prostatic adenocarcinoma and NEPC cell lines, an NEPC organoid line, and NEPC xenograft models to address the mechanistic basis of ENZ-induced NED, and to analyze suppression of NED and NEPC growth by PARP inhibition., Results: We identified an ENZ treatment-associated glucocorticoid receptor (GR)-MYCN-CDK5-RB1-E2F1 signaling pathway that drives NED in prostatic adenocarcinoma PDX and cell line models. Mechanistically, long-term ENZ treatment transcriptionally upregulates signaling of the GR-MYCN axis, leading to CDK5R1 and CDK5R2 upregulation, Rb1 phosphorylation, and N-Myc-mediated and E2F1-mediated NED gene expression. Importantly, olaparib (OLA) or talazoparib (TALA) suppressed these activities, and the combination of OLA and dinaciclib (DINA), an inhibitor of CDK2 and CDK5, which also inhibits Rb1 phosphorylation, suppressed NED and significantly improved therapeutic efficiency in NEPC cells in vitro and in NEPC tumors in vivo ., Conclusions: The results of our study indicate an important role of GR-MYCN-CDK5R1/2-RB1-NED signaling in ENZ-induced and PARP inhibitor-suppressed NEPC. We also demonstrated efficacy for OLA+DINA combination therapy in NEPC xenograft models., (©2019 American Association for Cancer Research.)

Published
2019
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42. Proteomic Features of Colorectal Cancer Identify Tumor Subtypes Independent of Oncogenic Mutations and Independently Predict Relapse-Free Survival.

Author

Clarke CN, Lee MS, Wei W, Manyam G, Jiang ZQ, Lu Y, Morris J, Broom B, Menter D, Vilar-Sanchez E, Raghav K, Eng C, Chang GJ, Simon I, Bernards R, Overman M, Mills GB, Maru D, and Kopetz S

Subjects
Cohort Studies, Colorectal Neoplasms genetics, Colorectal Neoplasms metabolism, Colorectal Neoplasms pathology, Female, Follow-Up Studies, Gene Expression Regulation, Neoplastic, Humans, Male, Middle Aged, Prognosis, Survival Rate, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Colorectal Neoplasms mortality, Mutation, Proteomics methods
Abstract

Background: The directed study of the functional proteome in colorectal cancer (CRC) has identified critical protein markers and signaling pathways; however, the prognostic relevance of many of these proteins remains unclear., Methods: We determined the prognostic implications of the functional proteome in 263 CRC tumor samples from patients treated at MD Anderson Cancer Center (MDACC) and 462 patients from The Cancer Genome Atlas (TCGA) to identify patterns of protein expression that drive tumorigenesis. A total of 163 validated proteins were analyzed by reverse phase protein array (RPPA). Unsupervised hierarchical clustering of the tumor proteins from the MDACC cohort was performed, and clustering was validated using RPPA data from TCGA CRC. Cox regression was used to identify predictors of tumor recurrence., Results: Clustering revealed dichotomization, with subtype A notable for a high epithelial-mesenchymal transition (EMT) protein signature, while subtype B was notable for high Akt/TSC/mTOR pathway components. Survival data were only available for the MDACC cohort and were used to evaluate prognostic relevance of these protein signatures. Group B demonstrated worse relapse-free survival (hazard ratio 2.11, 95% confidence interval 1.04-4.27, p = 0.039), although there was no difference in known genomic drivers between the two proteomic groups. Proteomic grouping and stage were significant predictors of recurrence on multivariate analysis. Eight proteins were found to be significant predictors of tumor recurrence on multivariate analysis: Collagen VI, FOXO3a, INPP4B, LcK, phospho-PEA15, phospho-PRAS40, Rad51, phospho-S6., Conclusion: CRC can be classified into distinct subtypes by proteomic features independent of common oncogenic driver mutations. Proteomic analysis has identified key biomarkers with prognostic importance, however these findings require further validation in an independent cohort.

Published
2017
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43. Targeting DNA Damage Response in Prostate Cancer by Inhibiting Androgen Receptor-CDC6-ATR-Chk1 Signaling.

Author

Karanika S, Karantanos T, Li L, Wang J, Park S, Yang G, Zuo X, Song JH, Maity SN, Manyam GC, Broom B, Aparicio AM, Gallick GE, Troncoso P, Corn PG, Navone N, Zhang W, Li S, and Thompson TC

Subjects
Animals, Apoptosis drug effects, Ataxia Telangiectasia Mutated Proteins metabolism, Biomarkers metabolism, Cell Cycle Checkpoints drug effects, Cell Line, Tumor, DNA Damage drug effects, DNA Replication drug effects, DNA-Binding Proteins metabolism, Humans, Male, Mice, Mice, Nude, Phosphorylation drug effects, Prostatic Neoplasms drug therapy, Signal Transduction drug effects, Thiophenes pharmacology, Urea analogs & derivatives, Urea pharmacology, Androgen Receptor Antagonists pharmacology, Cell Cycle Proteins metabolism, Checkpoint Kinase 1 metabolism, DNA Damage physiology, Nuclear Proteins metabolism, Prostatic Neoplasms metabolism, Receptors, Androgen metabolism
Abstract

Cell division cycle 6 (CDC6), an androgen receptor (AR) target gene, is implicated in regulating DNA replication and checkpoint mechanisms. CDC6 expression is increased during prostate cancer (PCa) progression and positively correlates with AR in PCa tissues. AR or CDC6 knockdown, together with AZD7762, a Chk1/2 inhibitor, results in decreased TopBP1-ATR-Chk1 signaling and markedly increased ataxia-telangiectasia-mutated (ATM) phosphorylation, a biomarker of DNA damage, and synergistically increases treatment efficacy. Combination treatment with the AR signaling inhibitor enzalutamide (ENZ) and the Chk1/2 inhibitor AZD7762 demonstrates synergy with regard to inhibition of AR-CDC6-ATR-Chk1 signaling, ATM phosphorylation induction, and apoptosis in VCaP (mutant p53) and LNCaP-C4-2b (wild-type p53) cells. CDC6 overexpression significantly reduced ENZ- and AZD7762-induced apoptosis. Additive or synergistic therapeutic activities are demonstrated in AR-positive animal xenograft models. These findings have important clinical implications, since they introduce a therapeutic strategy for AR-positive, metastatic, castration-resistant PCa, regardless of p53 status, through targeting AR-CDC6-ATR-Chk1 signaling., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Published
2017
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44. Phase I/II study of azacitidine and capecitabine/oxaliplatin (CAPOX) in refractory CIMP-high metastatic colorectal cancer: evaluation of circulating methylated vimentin.

Author

Overman MJ, Morris V, Moinova H, Manyam G, Ensor J, Lee MS, Eng C, Kee B, Fogelman D, Shroff RT, LaFramboise T, Mazard T, Feng T, Hamilton S, Broom B, Lutterbaugh J, Issa JP, Markowitz SD, and Kopetz S

Subjects
Adult, Aged, Azacitidine administration & dosage, Azacitidine adverse effects, Capecitabine administration & dosage, Capecitabine adverse effects, Colorectal Neoplasms blood, CpG Islands, DNA Methylation drug effects, Disease-Free Survival, Drug Resistance, Neoplasm drug effects, Female, Humans, Male, Middle Aged, Organoplatinum Compounds administration & dosage, Organoplatinum Compounds adverse effects, Oxaliplatin, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biomarkers, Tumor blood, Colorectal Neoplasms drug therapy, Vimentin blood
Abstract

Purpose: Hypermethylation of promoter CpG islands (CIMP) has been strongly implicated in chemotherapy resistance and is implicated in the pathogenesis of a subset of colorectal cancers (CRCs) termed CIMP-high., Experimental Design: This phase I/II study in CRC (phase II portion restricted to CIMP-high CRC), treated fluoropyrimidine/oxaliplatin refractory patients with azacitidine (75 mg/m2/day subcutaneously D1-5) and CAPOX (capecitibine and oxaliplatin) every three weeks., Results: Twenty-six patients (pts) were enrolled in this study: 15 pts (12 treated at MTD) in phase I and 11 pts in phase II. No dose limiting toxicities were observed. A total of 14 pts were CIMP-high. No responses were seen. CIMP-high status did not correlate with efficacy endpoints [stable disease (SD) or progression-free survival (PFS)] or baseline vimentin methylation level. Changes in vimentin methylation over time did not correlate with efficacy outcomes. Baseline methylated vimentin correlated with tumor volume (P<0.001) and higher levels of baseline methylation correlated with the obtainment of stable disease (P=0.04)., Conclusions: Azacitidine and CAPOX were well tolerated with high rates of stable disease in CIMP-high pts, but no objective responses. Serum methylated vimentin may be associated with benefit from a regimen including a hypomethylation agent, although this study is not able to separate a potential prognostic or predictive role for the biomarker.

Published
2016
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45. MET amplification in metastatic colorectal cancer: an acquired response to EGFR inhibition, not a de novo phenomenon.

Author

Raghav K, Morris V, Tang C, Morelli P, Amin HM, Chen K, Manyam GC, Broom B, Overman MJ, Shaw K, Meric-Bernstam F, Maru D, Menter D, Ellis LM, Eng C, Hong D, and Kopetz S

Subjects
Antibodies, Monoclonal therapeutic use, Antineoplastic Agents therapeutic use, Cell-Free Nucleic Acids chemistry, Cell-Free Nucleic Acids genetics, Cetuximab therapeutic use, Cohort Studies, Colorectal Neoplasms drug therapy, Colorectal Neoplasms pathology, Drug Resistance, Neoplasm genetics, ErbB Receptors antagonists & inhibitors, ErbB Receptors metabolism, Humans, In Situ Hybridization, Fluorescence, Liver Neoplasms secondary, Panitumumab, Proto-Oncogene Proteins c-met metabolism, Sequence Analysis, DNA, Colorectal Neoplasms genetics, ErbB Receptors genetics, Gene Amplification, Proto-Oncogene Proteins c-met genetics
Abstract

Background: MET amplification appears to be a predictive biomarker for MET inhibition. Prior studies reported a MET amplification rate of 9-18% in metastatic colorectal cancer (mCRC) but do not differentiate increased gene copy numbers due to chromosomal level aberrations from focal gene amplifications. Validation of MET amplification rate in mCRC is critical to this field., Results: In tumor tissue-based analyses, overall MET amplification rate was 1.7% (10/590). MET amplification was seen in 0/103 (0%), 4/208 (1.9%) and 6/279 (2.2%) cases, in cohorts 1, 2 and 3, respectively. Rate of MET amplification in cfDNA of cohort 4 patients refractory to anti-EGFR therapy (n = 53) was 22.6% (12/53) and was significantly higher compared to patients not exposed to anti-EGFR therapy (p < 0.001)., Materials and Methods: We analyzed MET amplification in mCRC (n = 795) using different methods across multiple cohorts. Cohort 1 (n = 103) and 2 (n = 208) included resected liver metastases and tumor biopsies, respectively, tested for MET amplification using fluorescence in-situ hybridization [amplification: MET/CEP7 ratio ≥ 2.0]. Using another tissue-based approach, cohort 3 (n = 279) included tumor biopsies sequenced with HiSeq (Illumina) with full exome coverage for MET [amplification: ≥ 4 copies identified by an in-house algorithm]. Using a blood-based approach by contrast, cohort 4 (n = 205) included patients in whom the full exome of MET in circulating-free DNA (cfDNA) was sequenced with HiSeq., Conclusions: Contrary to prior reports, in this large cohort, MET amplification was a rare event in mCRC tissues. In plasma by stark contrast, MET amplification identified by cfDNA occurred in a sizable subset of patients that are refractory to anti-EGFR therapy.

Published
2016
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46. Attitudes toward complementary and alternative medicine amongst oncology professionals in Brazil.

Author

Pamela S, Alex B, Vanessa B, Jon A, and Nelson Filice de B

Subjects
Brazil, Humans, Surveys and Questionnaires, Attitude of Health Personnel, Complementary Therapies psychology, Health Knowledge, Attitudes, Practice, Neoplasms therapy, Physicians psychology
Abstract

Complementary and alternative medicines (CAM) are popular amongst cancer patients in the Brazilian context, however little is known about oncology health professionals' attitudes toward the role of CAM and their perspectives on the potential for integration into oncological care. In this study, drawing on a series of interviews with oncology professionals (i.e. doctors, nurses, nutritionists, pharmacologists and psychologists), we provide insight into their views on the rise, validity, and role of CAM in cancer care. The results reveal two key dynamics in relation to CAM in cancer care in Brazil. First, that doctors, nurses and other allied professionals hold considerably different views on the value and place of CAM, and in turn ascribe it varying levels of legitimacy potentially limiting integration. Second, that while some health professionals may articulate a degree of support for CAM, this is limited by perceptions of CAM as lacking efficacy and intruding on their respective jurisdictional claims. Further research is needed in the Brazilian context to explore patient and professional perspectives on experiences on CAM in cancer care, including how oncology professionals' varying positions on CAM may influence what patients are prepared to use, or discuss, in the context of cancer care., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Published
2016
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47. Caveolin-1 regulates hormone resistance through lipid synthesis, creating novel therapeutic opportunities for castration-resistant prostate cancer.

Author

Karantanos T, Karanika S, Wang J, Yang G, Dobashi M, Park S, Ren C, Li L, Basourakos SP, Hoang A, Efstathiou E, Wang X, Troncoso P, Titus M, Broom B, Kim J, Corn PG, Logothetis CJ, and Thompson TC

Subjects
Acetyl-CoA Carboxylase metabolism, Animals, Fatty Acid Synthase, Type I metabolism, Humans, Male, Mice, Mice, Transgenic, Caveolin 1 metabolism, Gene Expression Regulation, Neoplastic physiology, Lipids biosynthesis, Prostatic Neoplasms, Castration-Resistant metabolism
Abstract

Caveolin-1 (Cav-1) is overexpressed in aggressive and metastatic prostate cancer (PCa) and induces PCa cell proliferation. Androgens mediate lipid synthesis through acetyl-CoA carboxylase-1 (ACC1) and fatty acid synthase (FASN). We investigated the Cav-1-mediated lipid synthesis in the development of castration resistance, and identified novel therapeutic opportunities. Using the PBCre+;Ptenloxp/loxp;PBCav-1+ mouse model we found that Cav-1 induction increased cancer incidence and growth, and ACC1-FASN expression in intact and castrated mice. We demonstrated that Cav-1 regulated ACC1 and FASN expression in an AR-independent way and increased palmitate synthesis using western blot analysis, qRT-PCR and mass spectrometry in vitro. By using FASN siRNA and C-75, we found that FASN inhibition was more effective in Cav-1-overexpressing cells. This inhibition was abrogated by ACC1si RNA, revealing the role of malonyl-CoA, an ACC1 product, as a mediator of cytotoxicity. Cav-1 was associated with ACC1 in human tumors and ACC1, FASN, and Cav-1 expression were increased in metastatic PCa compared to primary tumors and normal prostate epithelium. Palmitoleate and oleate levels were higher in BMA from patients with metastatic PCa who responded poorly to abiraterone acetate. Our findings suggest that Cav-1 promotes hormone resistance through the upregulation of ACC1-FASN and lipid synthesis under androgen deprivation, suggesting that FASN inhibition could be used to treat PCa that demonstrates Cav-1 overexpression., Competing Interests: The authors declare that they have no conflict of interest

Published
2016
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48. Combined Tumor Suppressor Defects Characterize Clinically Defined Aggressive Variant Prostate Cancers.

Author

Aparicio AM, Shen L, Tapia EL, Lu JF, Chen HC, Zhang J, Wu G, Wang X, Troncoso P, Corn P, Thompson TC, Broom B, Baggerly K, Maity SN, and Logothetis CJ

Subjects
Biomarkers, Tumor, Biopsy, Cluster Analysis, DNA Copy Number Variations, Disease Progression, Gene Expression Profiling, Humans, Immunohistochemistry, Male, Mutation, Neoplasm Staging, Prostatic Neoplasms metabolism, Prostatic Neoplasms therapy, Receptors, Androgen genetics, Receptors, Androgen metabolism, Signal Transduction, Tumor Suppressor Proteins metabolism, Prostatic Neoplasms diagnosis, Prostatic Neoplasms genetics, Tumor Suppressor Proteins genetics
Abstract

Purpose: Morphologically heterogeneous prostate cancers that behave clinically like small-cell prostate cancers (SCPC) share their chemotherapy responsiveness. We asked whether these clinically defined, morphologically diverse, "aggressive variant prostate cancer (AVPC)" also share molecular features with SCPC., Experimental Design: Fifty-nine prostate cancer samples from 40 clinical trial participants meeting AVPC criteria, and 8 patient-tumor derived xenografts (PDX) from 6 of them, were stained for markers aberrantly expressed in SCPC. DNA from 36 and 8 PDX was analyzed by Oncoscan for copy number gains (CNG) and losses (CNL). We used the AVPC PDX to expand observations and referenced publicly available datasets to arrive at a candidate molecular signature for the AVPC., Results: Irrespective of morphology, Ki67 and Tp53 stained ≥10% cells in 80% and 41% of samples, respectively. RB1 stained <10% cells in 61% of samples and AR in 36%. MYC (surrogate for 8q) CNG and RB1 CNL showed in 54% of 44 samples each and PTEN CNL in 48%. All but 1 of 8 PDX bore Tp53 missense mutations. RB1 CNL was the strongest discriminator between unselected castration-resistant prostate cancer (CRPC) and the AVPC. Combined alterations in RB1, Tp53, and/or PTEN were more frequent in the AVPC than in unselected CRPC and in The Cancer Genome Atlas samples., Conclusions: Clinically defined AVPC share molecular features with SCPC and are characterized by combined alterations in RB1, Tp53, and/or PTEN., (©2015 American Association for Cancer Research.)

Published
2016
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49. TCGASpliceSeq a compendium of alternative mRNA splicing in cancer.

Author

Ryan M, Wong WC, Brown R, Akbani R, Su X, Broom B, Melott J, and Weinstein J

Subjects
RNA, Messenger metabolism, Alternative Splicing, Databases, Nucleic Acid, Gene Expression Regulation, Neoplastic, Neoplasms genetics
Abstract

TCGA's RNASeq data represent one of the largest collections of cancer transcriptomes ever assembled. RNASeq technology, combined with computational tools like our SpliceSeq package, provides a comprehensive, detailed view of alternative mRNA splicing. Aberrant splicing patterns in cancers have been implicated in such processes as carcinogenesis, de-differentiation and metastasis. TCGA SpliceSeq (http://bioinformatics.mdanderson.org/TCGASpliceSeq) is a web-based resource that provides a quick, user-friendly, highly visual interface for exploring the alternative splicing patterns of TCGA tumors. Percent Spliced In (PSI) values for splice events on samples from 33 different tumor types, including available adjacent normal samples, have been loaded into TCGA SpliceSeq. Investigators can interrogate genes of interest, search for the genes that show the strongest variation between or among selected tumor types, or explore splicing pattern changes between tumor and adjacent normal samples. The interface presents intuitive graphical representations of splicing patterns, read counts and various statistical summaries, including percent spliced in. Splicing data can also be downloaded for inclusion in integrative analyses. TCGA SpliceSeq is freely available for academic, government or commercial use., (© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Published
2016
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50. Treating chronic spontaneous urticaria using a brief 'whole person' treatment approach: a proof-of-concept study.

Author

Lindsay K, Goulding J, Solomon M, and Broom B

Abstract

Background: Chronic spontaneous urticaria (CSU) poses problems with respect to high prevalence, reduced quality of life, lack of long term efficacy, and expense of current treatments for severe intractable symptoms. There have been many reports suggesting 'stress' factors may be implicated, but there are no studies that explore the efficacy of treatments including a psychological perspective. A whole person treatment approach (WPTA), which addresses psychological factors has been used, with effect, for 6 years in the Auckland City Hospital Immunology Department., Findings: In a pilot study to demonstrate feasibility of recruitment and treatment of CSU patients in a time-limited, whole person treatment approach, within a conventional immunology department, four patients (three CSU and one idiopathic angioedema) were recruited into a brief WPTA course based in non-dualistic concepts of mind and body connectedness, and utilising psychotherapy-derived listening skills for up to 10 h long sessions, once per week. Treatment efficacy rating, using Urticaria Activity Score and the Urticaria Severity Score, and reduction of drug usage, showed patients experienced long term resolution of urticaria and cessation of hospitalisation for angioedema and came off regular antihistamine medication., Conclusions: A clinician treating chronic spontaneous urticaria in an Immunology department, using a whole person treatment paradigm, can safely explore unique meanings and emotional states, in a process acceptable to patients, resulting in a significant clinical benefit for symptoms. A much larger study comparing the outcome of WPTA versus standard treatment alone is warranted.

Published
2015
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