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18 results on '"Buda, E."'

1. Comprehensive genomic characterization of head and neck squamous cell carcinomas

Author

Lawrence, MS, Sougnez, C, Lichtenstein, L, Cibulskis, K, Lander, E, Gabriel, SB, Getz, G, Ally, A, Balasundaram, M, Birol, I, Bowlby, R, Brooks, D, Butterfield, YSN, Carlsen, R, Cheng, D, Chu, A, Dhalla, N, Guin, R, Holt, RA, Jones, SJM, Lee, D, Li, HI, Marra, MA, Mayo, M, Moore, RA, Mungall, AJ, Robertson, AG, Schein, JE, Sipahimalani, P, Tam, A, Thiessen, N, Wong, T, Protopopov, A, Santoso, N, Lee, S, Parfenov, M, Zhang, J, Mahadeshwar, HS, Tang, J, Ren, X, Seth, S, Haseley, P, Zeng, D, Yang, L, Xu, AW, Song, X, Pantazi, A, Bristow, CA, Hadjipanayis, A, Seidman, J, Chin, L, Park, PJ, Kucherlapati, R, Akbani, R, Casasent, T, Liu, W, Lu, Y, Mills, G, Motter, T, Weinstein, J, Diao, L, Wang, J, Hong Fan, Y, Liu, J, Wang, K, Auman, JT, Balu, S, Bodenheimer, T, Buda, E, Hayes, DN, Hoadley, KA, Hoyle, AP, Jefferys, SR, Jones, CD, Kimes, PK, Liu, Y, Marron, JS, Meng, S, Mieczkowski, PA, Mose, LE, Parker, JS, Perou, CM, Prins, JF, Roach, J, Shi, Y, Simons, JV, Singh, D, Soloway, MG, Tan, D, Veluvolu, U, Walter, V, Waring, S, Wilkerson, MD, and Wu, J

Abstract

© 2015 Macmillan Publishers Limited. All rights reserved. The Cancer Genome Atlas profiled 279 head and neck squamous cell carcinomas (HNSCCs) to provide a comprehensive landscape of somatic genomic alterations. Here we show that human-papillomavirus-associated tumours are dominated by helical domain mutations of the oncogene PIK3CA, novel alterations involving loss of TRAF3, and amplification of the cell cycle gene E2F1. Smoking-related HNSCCs demonstrate near universal loss-of-function TP53 mutations and CDKN2A inactivation with frequent copy number alterations including amplification of 3q26/28 and 11q13/22. A subgroup of oral cavity tumours with favourable clinical outcomes displayed infrequent copy number alterations in conjunction with activating mutations of HRAS or PIK3CA, coupled with inactivating mutations of CASP8, NOTCH1 and TP53. Other distinct subgroups contained loss-of-function alterations of the chromatin modifier NSD1, WNT pathway genes AJUBA and FAT1, and activation of oxidative stress factor NFE2L2, mainly in laryngeal tumours. Therapeutic candidate alterations were identified in most HNSCCs.

Published
2015

2. Integrated genomic characterization of endometrial carcinoma

Author

Getz, G, Gabriel, SB, Cibulskis, K, Lander, E, Sivachenko, A, Sougnez, C, Lawrence, M, Kandoth, C, Dooling, D, Fulton, R, Fulton, L, Kalicki-Veizer, J, McLellan, MD, O'Laughlin, M, Schmidt, H, Wilson, RK, Ye, K, Li, D, Ally, A, Balasundaram, M, Birol, I, Butterfield, YSN, Carlsen, R, Carter, C, Chu, A, Chuah, E, Chun, HJE, Dhalla, N, Guin, R, Hirst, C, Holt, RA, Jones, SJM, Lee, D, Li, HI, Marra, MA, Mayo, M, Moore, RA, Mungall, AJ, Plettner, P, Schein, JE, Sipahimalani, P, Tam, A, Varhol, RJ, Gordon Robertson, A, Cherniack, AD, Pashtan, I, Saksena, G, Onofrio, RC, Schumacher, SE, Tabak, B, Carter, SL, Hernandez, B, Gentry, J, Salvesen, HB, Ardlie, K, Winckler, W, Beroukhim, R, Meyerson, M, Hadjipanayis, A, Lee, S, Mahadeshwar, HS, Park, P, Protopopov, A, Ren, X, Seth, S, Song, X, Tang, J, Xi, R, Yang, L, Dong, Z, Kucherlapati, R, Chin, L, Zhang, J, Todd Auman, J, Balu, S, Bodenheimer, T, Buda, E, Neil Hayes, D, Hoyle, AP, Jefferys, SR, Jones, CD, Meng, S, Mieczkowski, PA, Mose, LE, Parker, JS, and Perou, CM

Subjects
endocrine system diseases
Abstract

We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array-and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours. © 2013 Macmillan Publishers Limited. All rights reserved.

Published
2013

3. 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

4. The cancer genome atlas pan-cancer analysis project

Author

Weinstein, J., Collisson, E., Mills, G., Shaw, K., Ozenberger, B., Ellrott, K., Sander, C., Stuart, J., Chang, K., Creighton, C., Davis, C., Donehower, L., Drummond, J., Wheeler, D., Ally, A., Balasundaram, M., Birol, I., Butterfield, Y., Chu, A., Chuah, E., Chun, H., Dhalla, N., Guin, R., Hirst, M., Hirst, C., Holt, R., Jones, S., Lee, D., Li, H., Marra, M., Mayo, M., Moore, R., Mungall, A., Robertson, A., Schein, J., Sipahimalani, P., Tam, A., Thiessen, N., Varhol, Richard, Beroukhim, R., Bhatt, A., Brooks, A., Cherniack, A., Freeman, S., Gabriel, S., Helman, E., Jung, J., Meyerson, M., Ojesina, A., Pedamallu, C., Saksena, G., Schumacher, S., Tabak, B., Zack, T., Lander, E., Bristow, C., Hadjipanayis, A., Haseley, P., Kucherlapati, R., Lee, S., Lee, E., Luquette, L., Mahadeshwar, H., Pantazi, A., Parfenov, M., Park, P., Protopopov, A., Ren, X., Santoso, N., Seidman, J., Seth, S., Song, X., Tang, J., Xi, R., Xu, A., Yang, L., Zeng, D., Auman, J., Balu, S., Buda, E., Weinstein, J., Collisson, E., Mills, G., Shaw, K., Ozenberger, B., Ellrott, K., Sander, C., Stuart, J., Chang, K., Creighton, C., Davis, C., Donehower, L., Drummond, J., Wheeler, D., Ally, A., Balasundaram, M., Birol, I., Butterfield, Y., Chu, A., Chuah, E., Chun, H., Dhalla, N., Guin, R., Hirst, M., Hirst, C., Holt, R., Jones, S., Lee, D., Li, H., Marra, M., Mayo, M., Moore, R., Mungall, A., Robertson, A., Schein, J., Sipahimalani, P., Tam, A., Thiessen, N., Varhol, Richard, Beroukhim, R., Bhatt, A., Brooks, A., Cherniack, A., Freeman, S., Gabriel, S., Helman, E., Jung, J., Meyerson, M., Ojesina, A., Pedamallu, C., Saksena, G., Schumacher, S., Tabak, B., Zack, T., Lander, E., Bristow, C., Hadjipanayis, A., Haseley, P., Kucherlapati, R., Lee, S., Lee, E., Luquette, L., Mahadeshwar, H., Pantazi, A., Parfenov, M., Park, P., Protopopov, A., Ren, X., Santoso, N., Seidman, J., Seth, S., Song, X., Tang, J., Xi, R., Xu, A., Yang, L., Zeng, D., Auman, J., Balu, S., and Buda, E.

Abstract

The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.

Published
2013

5. Comprehensivemolecular characterization of clear cell renal cell carcinoma

Author

Creighton, C., Morgan, M., Gunaratne, P., Wheeler, D., Gibbs, R., Robertson, A., Chu, A., Beroukhim, R., Cibulskis, K., Signoretti, S., Vandin, F., Wu, H., Raphael, B., Verhaak, R., Tamboli, P., Torres-Garcia, W., Akbani, R., Weinstein, J., Reuter, V., Hsieh, J., Brannon, A., Hakimi, A., Jacobsen, A., Ciriello, G., Reva, B., Ricketts, C., Linehan, W., Stuart, J., Rathmell, W., Shen, H., Laird, P., Muzny, D., Davis, C., Xi, L., Chang, K., Kakkar, N., Trevino, L., Benton, S., Reid, J., Morton, D., Doddapaneni, H., Han, Y., Lewis, L., Dinh, H., Kovar, C., Zhu, Y., Santibanez, J., Wang, M., Hale, W., Kalra, D., Getz, G., Lawrence, M., Sougnez, C., Carter, S., Sivachenko, A., Lichtenstein, L., Stewart, C., Voet, D., Fisher, S., Gabriel, S., Lander, E., Schumacher, S., Tabak, B., Saksena, G., Onofrio, R., Cherniack, A., Gentry, J., Ardlie, K., Meyerson, M., Chun, H., Mungall, A., Sipahimalani, P., Stoll, D., Ally, A., Balasundaram, M., Butterfield, Y., Carlsen, R., Carter, C., Chuah, E., Coope, R., Dhalla, N., Gorski, S., Guin, R., Hirst, C., Hirst, M., Holt, R., Lebovitz, C., Lee, D., Li, H., Mayo, M., Moore, R., Pleasance, E., Plettner, P., Schein, J., Shafiei, A., Slobodan, J., Tam, A., Thiessen, N., Varhol, Richard, Wye, N., Zhao, Y., Birol, I., Jones, S., Marra, M., Auman, J., Tan, D., Jones, C., Hoadley, K., Mieczkowski, P., Mose, L., Jefferys, S., Topal, M., Liquori, C., Turman, Y., Shi, Y., Waring, S., Buda, E., Walsh, J., Wu, J., Bodenheimer, T., Hoyle, A., Simons, J., Soloway, M., Balu, S., Parker, J., Hayes, D., Perou, C., Kucherlapati, R., Park, P., Triche, T., Weisenberger, D., Lai, P., Bootwalla, M., Maglinte, D., Mahurkar, S., Berman, B., Van den Berg, D., Cope, L., Baylin, S., Noble, M., DiCara, D., Zhang, H., Cho, J., Heiman, D., Gehlenborg, N., Mallard, W., Lin, P., Frazer, S., Stojanov, P., Liu, Y., Zhou, L., Kim, J., Chin, L., Benz, C., Yau, C., Reynolds, S., Shmulevich, I., Vegesna, R., Kim, H., Zhang, W., Cogdell, D., Jonasch, E., Ding, Z., Lu, Y., Zhang, N., Unruh, A., Casasent, T., Wakefield, C., Tsavachidou, D., Mills, G., Schultz, N., Antipin, Y., Gao, J., Cerami, E., Gross, B., Aksoy, B., Sinha, R., Weinhold, N., Sumer, S., Taylor, B., Shen, R., Ostrovnaya, I., Berger, M., Ladanyi, M., Sander, C., Fei, S., Stout, A., Spellman, P., Rubin, D., Liu, T., Sam, N., Paull, E., Carlin, D., Goldstein, T., Waltman, P., Ellrott, K., Zhu, J., Haussler, D., Xiao, W., Shelton, C., Gardner, J., Penny, R., Sherman, M., Mallery, D., Morris, S., Paulauskis, J., Burnett, K., Shelton, T., Kaelin, W., Choueiri, T., Atkins, M., Curley, E., Tickoo, S., Thorne, L., Boice, L., Huang, M., Fisher, J., Vocke, C., Peterson, J., Worrell, R., Merino, M., Schmidt, L., Czerniak, B., Aldape, K., Wood, C., Boyd, J., Weaver, J., Iacocca, M., Petrelli, N., Witkin, G., Brown, J., Czerwinski, C., Huelsenbeck-Dill, L., Rabeno, B., Myers, J., Morrison, C., Bergsten, J., Eckman, J., Harr, J., Smith, C., Tucker, K., Zach, L., Bshara, W., Gaudioso, C., Dhir, R., Maranchie, J., Nelson, J., Parwani, A., Potapova, O., Fedosenko, K., Cheville, J., Thompson, R., Mosquera, J., Rubin, M., Blute, M., Pihl, T., Jensen, M., Sfeir, R., Kahn, A., Kothiyal, P., Snyder, E., Pontius, J., Ayala, B., Backus, M., Walton, J., Baboud, J., Berton, D., Nicholls, M., Srinivasan, D., Raman, R., Girshik, S., Kigonya, P., Alonso, S., Sanbhadti, R., Barletta, S., Pot, D., Sheth, M., Demchok, J., Davidsen, T., Wang, Z., Yang, L., Tarnuzzer, R., Zhang, J., Eley, G., Ferguson, M., Shaw, K., Guyer, M., Ozenberger, B., Sofia, H., Creighton, C., Morgan, M., Gunaratne, P., Wheeler, D., Gibbs, R., Robertson, A., Chu, A., Beroukhim, R., Cibulskis, K., Signoretti, S., Vandin, F., Wu, H., Raphael, B., Verhaak, R., Tamboli, P., Torres-Garcia, W., Akbani, R., Weinstein, J., Reuter, V., Hsieh, J., Brannon, A., Hakimi, A., Jacobsen, A., Ciriello, G., Reva, B., Ricketts, C., Linehan, W., Stuart, J., Rathmell, W., Shen, H., Laird, P., Muzny, D., Davis, C., Xi, L., Chang, K., Kakkar, N., Trevino, L., Benton, S., Reid, J., Morton, D., Doddapaneni, H., Han, Y., Lewis, L., Dinh, H., Kovar, C., Zhu, Y., Santibanez, J., Wang, M., Hale, W., Kalra, D., Getz, G., Lawrence, M., Sougnez, C., Carter, S., Sivachenko, A., Lichtenstein, L., Stewart, C., Voet, D., Fisher, S., Gabriel, S., Lander, E., Schumacher, S., Tabak, B., Saksena, G., Onofrio, R., Cherniack, A., Gentry, J., Ardlie, K., Meyerson, M., Chun, H., Mungall, A., Sipahimalani, P., Stoll, D., Ally, A., Balasundaram, M., Butterfield, Y., Carlsen, R., Carter, C., Chuah, E., Coope, R., Dhalla, N., Gorski, S., Guin, R., Hirst, C., Hirst, M., Holt, R., Lebovitz, C., Lee, D., Li, H., Mayo, M., Moore, R., Pleasance, E., Plettner, P., Schein, J., Shafiei, A., Slobodan, J., Tam, A., Thiessen, N., Varhol, Richard, Wye, N., Zhao, Y., Birol, I., Jones, S., Marra, M., Auman, J., Tan, D., Jones, C., Hoadley, K., Mieczkowski, P., Mose, L., Jefferys, S., Topal, M., Liquori, C., Turman, Y., Shi, Y., Waring, S., Buda, E., Walsh, J., Wu, J., Bodenheimer, T., Hoyle, A., Simons, J., Soloway, M., Balu, S., Parker, J., Hayes, D., Perou, C., Kucherlapati, R., Park, P., Triche, T., Weisenberger, D., Lai, P., Bootwalla, M., Maglinte, D., Mahurkar, S., Berman, B., Van den Berg, D., Cope, L., Baylin, S., Noble, M., DiCara, D., Zhang, H., Cho, J., Heiman, D., Gehlenborg, N., Mallard, W., Lin, P., Frazer, S., Stojanov, P., Liu, Y., Zhou, L., Kim, J., Chin, L., Benz, C., Yau, C., Reynolds, S., Shmulevich, I., Vegesna, R., Kim, H., Zhang, W., Cogdell, D., Jonasch, E., Ding, Z., Lu, Y., Zhang, N., Unruh, A., Casasent, T., Wakefield, C., Tsavachidou, D., Mills, G., Schultz, N., Antipin, Y., Gao, J., Cerami, E., Gross, B., Aksoy, B., Sinha, R., Weinhold, N., Sumer, S., Taylor, B., Shen, R., Ostrovnaya, I., Berger, M., Ladanyi, M., Sander, C., Fei, S., Stout, A., Spellman, P., Rubin, D., Liu, T., Sam, N., Paull, E., Carlin, D., Goldstein, T., Waltman, P., Ellrott, K., Zhu, J., Haussler, D., Xiao, W., Shelton, C., Gardner, J., Penny, R., Sherman, M., Mallery, D., Morris, S., Paulauskis, J., Burnett, K., Shelton, T., Kaelin, W., Choueiri, T., Atkins, M., Curley, E., Tickoo, S., Thorne, L., Boice, L., Huang, M., Fisher, J., Vocke, C., Peterson, J., Worrell, R., Merino, M., Schmidt, L., Czerniak, B., Aldape, K., Wood, C., Boyd, J., Weaver, J., Iacocca, M., Petrelli, N., Witkin, G., Brown, J., Czerwinski, C., Huelsenbeck-Dill, L., Rabeno, B., Myers, J., Morrison, C., Bergsten, J., Eckman, J., Harr, J., Smith, C., Tucker, K., Zach, L., Bshara, W., Gaudioso, C., Dhir, R., Maranchie, J., Nelson, J., Parwani, A., Potapova, O., Fedosenko, K., Cheville, J., Thompson, R., Mosquera, J., Rubin, M., Blute, M., Pihl, T., Jensen, M., Sfeir, R., Kahn, A., Kothiyal, P., Snyder, E., Pontius, J., Ayala, B., Backus, M., Walton, J., Baboud, J., Berton, D., Nicholls, M., Srinivasan, D., Raman, R., Girshik, S., Kigonya, P., Alonso, S., Sanbhadti, R., Barletta, S., Pot, D., Sheth, M., Demchok, J., Davidsen, T., Wang, Z., Yang, L., Tarnuzzer, R., Zhang, J., Eley, G., Ferguson, M., Shaw, K., Guyer, M., Ozenberger, B., and Sofia, H.

Abstract

Genetic changes underlying clear cell renal cell carcinoma(ccRCC) include alterations in genes controlling cellularoxygen sensing (for example, VHL) and the maintenance of chromatin states (for example, PBRM1). We surveyed more than 400 tumours using different genomic platforms and identified 19 significantly mutated genes. The PI(3)K/AKT pathway was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodelling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving downregulation of genes involved in the TCA cycle, decreasedAMPK and PTEN protein levels, upregulation of the pentose phosphate pathway and the glutamine transporter genes, increased acetyl-CoA carboxylase protein, and altered promoter methylation of miR-21 (also known as MIR21) and GRB10. Remodelling cellular metabolism thus constitutes a recurrent pattern in ccRCC that correlates with tumour stage and severity and offers new views on the opportunities for disease treatment. © 2013 Macmillan Publishers Limited. All rights reserved.

Published
2013

6. Integrated genomic characterization of endometrial carcinoma

Author

Getz, G., Gabriel, S., Cibulskis, K., Lander, E., Sivachenko, A., Sougnez, C., Lawrence, M., Kandoth, C., Dooling, D., Fulton, R., Fulton, L., Kalicki-Veizer, J., McLellan, M., O'Laughlin, M., Schmidt, H., Wilson, R., Ye, K., Li, D., Ally, A., Balasundaram, M., Birol, I., Butterfield, Y., Carlsen, R., Carter, C., Chu, A., Chuah, E., Chun, H., Dhalla, N., Guin, R., Hirst, C., Holt, R., Jones, S., Lee, D., Li, H., Marra, M., Mayo, M., Moore, R., Mungall, A., Plettner, P., Schein, J., Sipahimalani, P., Tam, A., Varhol, Richard, Gordon Robertson, A., Cherniack, A., Pashtan, I., Saksena, G., Onofrio, R., Schumacher, S., Tabak, B., Carter, S., Hernandez, B., Gentry, J., Salvesen, H., Ardlie, K., Winckler, W., Beroukhim, R., Meyerson, M., Hadjipanayis, A., Lee, S., Mahadeshwar, H., Park, P., Protopopov, A., Ren, X., Seth, S., Song, X., Tang, J., Xi, R., Yang, L., Dong, Z., Kucherlapati, R., Chin, L., Zhang, J., Todd Auman, J., Balu, S., Bodenheimer, T., Buda, E., Neil Hayes, D., Hoyle, A., Jefferys, S., Jones, C., Meng, S., Mieczkowski, P., Mose, L., Parker, J., Perou, C., Getz, G., Gabriel, S., Cibulskis, K., Lander, E., Sivachenko, A., Sougnez, C., Lawrence, M., Kandoth, C., Dooling, D., Fulton, R., Fulton, L., Kalicki-Veizer, J., McLellan, M., O'Laughlin, M., Schmidt, H., Wilson, R., Ye, K., Li, D., Ally, A., Balasundaram, M., Birol, I., Butterfield, Y., Carlsen, R., Carter, C., Chu, A., Chuah, E., Chun, H., Dhalla, N., Guin, R., Hirst, C., Holt, R., Jones, S., Lee, D., Li, H., Marra, M., Mayo, M., Moore, R., Mungall, A., Plettner, P., Schein, J., Sipahimalani, P., Tam, A., Varhol, Richard, Gordon Robertson, A., Cherniack, A., Pashtan, I., Saksena, G., Onofrio, R., Schumacher, S., Tabak, B., Carter, S., Hernandez, B., Gentry, J., Salvesen, H., Ardlie, K., Winckler, W., Beroukhim, R., Meyerson, M., Hadjipanayis, A., Lee, S., Mahadeshwar, H., Park, P., Protopopov, A., Ren, X., Seth, S., Song, X., Tang, J., Xi, R., Yang, L., Dong, Z., Kucherlapati, R., Chin, L., Zhang, J., Todd Auman, J., Balu, S., Bodenheimer, T., Buda, E., Neil Hayes, D., Hoyle, A., Jefferys, S., Jones, C., Meng, S., Mieczkowski, P., Mose, L., Parker, J., and Perou, C.

Abstract

We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array-and sequencing-based technologies. Uterine serous tumours and ~25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours. © 2013 Macmillan Publishers Limited. All rights reserved.

Published
2013

11. 4-Mb MOSFET-selected phase-change memory experimental chip

Author

Bedeschi, F., primary, Bez, R., additional, Boffino, C., additional, Bonizzoni, E., additional, Buda, E., additional, Casagrande, G., additional, Costa, L., additional, Ferraro, M., additional, Gastaldi, R., additional, Khouri, O., additional, Ottogalli, F., additional, Pellizzer, F., additional, Pirovano, A., additional, Resta, C., additional, Torelli, G., additional, and Tosi, M., additional

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12. An 8Mb demonstrator for high-density 1.8V Phase-Change Memories

Author

Bedeschi, F., primary, Resta, C., additional, Khouri, O., additional, Buda, E., additional, Costa, L., additional, Ferraro, M., additional, Pellizzer, F., additional, Ottogalli, F., additional, Pirovano, A., additional, Tosi, M., additional, Bez, R., additional, Gastaldi, R., additional, and Casagrande, G., additional

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13. Comprehensive molecular profiling of lung adenocarcinoma

Author

Amie Radenbaugh, Noreen Dhalla, Christina Williamson, Charles Saller, James Suh, Ramaswamy Govindan, Travis I. Zack, Paul T. Spellman, Daniel DiCara, Harvey I. Pass, Deepak Srinivasan, William G. Richards, Robert J. Cerfolio, Igor Letovanec, A. Gordon Robertson, Gabriel Sica, Chad J. Creighton, Hendrik Dienemann, Jeffrey A. Borgia, Boris Reva, Bryan F. Meyers, Yiling Lu, Nikolaus Schultz, Christopher I. Amos, Dante Trusty, Carmelo Gaudioso, Michael Meister, James T. Robinson, Lihua Zou, James Shin, Jeremy Parfitt, Darlene Lee, Junyuan Wu, Carl Morrison, Scott L. Carter, Giovanni Ciriello, Nils Weinhold, Elena Nemirovich-Danchenko, Andrew Wei Xu, Christopher G. Maher, Lori Boice, Irina Zaytseva, Dennis A. Wigle, Kenna R. Mills Shaw, Matthew G. Soloway, Matthew Meyerson, Peng Chieh Chen, Frank Schneider, Troy Shelton, Douglas Voet, Steven E. Schumacher, D L Rotin, Saianand Balu, Stuart R. Jefferys, Tom Bodenheimer, Bradley A. Ozenberger, Eric S. Lander, Edward Gabrielson, Konstantin V. Fedosenko, Rehan Akbani, William D. Travis, Ari B. Kahn, Marcin Imielinski, Jacqueline E. Schein, Thomas L. Bauer, Kai Ye, Samuel A. Yousem, Robert C. Onofrio, Thomas Muley, Ayesha S. Bryant, Michael K. Asiedu, Monique Albert, Pei Lin, Corbin D. Jones, Edwina Duhig, Jean C. Zenklusen, Lucinda Fulton, Christina Yau, J. Todd Auman, Leigh B. Thorne, Elena Helman, Richard T. Cheney, William Lee, Patrick K. Kimes, Juok Cho, Alexei Protopopov, Wenbin Liu, Lee Lichtenstein, Jing Wang, Lixing Yang, W. Kimryn Rathmell, Jo Ellen Weaver, David A. Wheeler, Leslie Cope, Mark A. Watson, Heidi J. Sofia, Angeliki Pantazi, Ronglai Shen, Jeffrey Roach, Eric A. Collisson, Patrick Kwok Shing Ng, Angela Hadjipanayis, Peter S. Hammerman, David Van Den Berg, Kwun M. Fong, Nils Gehlenborg, Natasha Rekhtman, William K. Funkhouser, D. Neil Hayes, Harshad S. Mahadeshwar, Semin Lee, Martin Peifer, David Mallery, Piotr A. Mieczkowski, Ranabir Guin, Madhusmita Behera, Philipp A. Schnabel, Jill M. Siegfried, Carmen Gomez-Fernandez, Johanna Gardner, Lynn M. Herbert, Hailei Zhang, Robert S. Fulton, Travis Sullivan, Sahil Seth, Sam Ng, Chandra Sekhar Pedamallu, Barry S. Taylor, Venkatraman E. Seshan, Valerie W. Rusch, Jinze Liu, Daniel P. Raymond, Jianjiong Gao, Nathan A. Pennell, Marco A. Marra, Jan F. Prins, Payal Sipahimalani, Janae V. Simons, Joel S. Parker, Rileen Sinha, Lindy Hunter, Raju Kucherlapati, Dennis T. Maglinte, Fedor Moiseenko, Eric E. Snyder, Roy Tarnuzzer, Beverly Lee, James Stephen Marron, Kristian Cibulskis, Jerome Myers, Haiyan I. Li, Robert Penny, Hartmut Juhl, Richard K. Wilson, Zhining Wang, Eran Hodis, Carrie Sougnez, Jiabin Tang, William Mallard, Bryan Hernandez, Liming Yang, Jennifer Brown, Gad Getz, Farhad Kosari, Catrina Fronick, Juliann Chmielecki, Jianhua Zhang, Suresh S. Ramalingam, Michael Parfenov, Peter J. Park, Tanja Davidsen, Philip H. Lai, Jeff Boyd, Dang Huy Quoc Thinh, Harmanjatinder S. Sekhon, Malcolm V. Brock, Mark Pool, Margi Sheth, Kimberly M. Rieger-Christ, Michael J. Liptay, E. Getz, S. Onur Sumer, Ian A. Yang, B. Arman Aksoy, Douglas B. Flieder, Bradley M. Broom, Carrie Hirst, Solange Peters, Joshua M. Stuart, Khurram Z. Khan, Scott Morris, Donghui Tan, Andrew J. Mungall, Ming-Sound Tsao, Gordon B. Mills, Stephen B. Baylin, Rebecca Carlsen, Sanja Dacic, Julien Baboud, Brenda Rabeno, Richard A. Hajek, Lauren Averett Byers, Yaron S.N. Butterfield, Miruna Balasundaram, Chip Stewart, Katherine Tarvin, Peter B. Illei, James G. Herman, David J. Kwiatkowski, Andy Chu, David Haussler, Natasja Wye, Charles M. Perou, Peter W. Laird, Timothy J. Triche, Yan Shi, Jill P. Mesirov, Angela N. Brooks, Lori Huelsenbeck-Dill, Steven J.M. Jones, Antonia H. Holway, Lixia Diao, Anthony A. Gal, David G. Beer, Angela Tam, Ashley H. Salazar, Mark A. Jensen, Robert A. Holt, Katherine A. Hoadley, John A. Demchok, Sandra McDonald, Chandra Goparaju, David Pot, Belinda E. Clarke, Gordon Robertson, Michael C. Wendl, Helga Thorvaldsdottir, Kristen Rogers, Joshua D. Campbell, Chris Sander, Rayleen V. Bowman, Marc Danie Nazaire, Michael Mayo, Olga Voronina, Ludmila Danilova, Paul Zippile, Netty Santoso, John V. Heymach, Matthew D. Wilkerson, John Eckman, Morgan Windsor, Cureline Oleg Dolzhanskiy, Nina Thiessen, Mara Rosenberg, Gideon Dresdner, Levi A. Garraway, Eric Chuah, Richard Varhol, Elizabeth Buda, Li Ding, Alice H. Berger, Xingzhi Song, John M. S. Bartlett, Michael D. McLellan, Olga Potapova, Joseph Paulauskis, Igor Jurisica, Benjamin Gross, Jaegil Kim, John N. Weinstein, Kevin Lau, Christopher R. Cabanski, Philip Bonomi, Michael S. Noble, Maureen F. Zakowski, George E. Sandusky, Mary Iacocca, Eric J. Burks, Erin Curley, Lynda Chin, Rajiv Dhir, Singer Ma, Sophie C. Egea, Umadevi Veluvolu, Sugy Kodeeswaran, Christopher A. Miller, Moiz S. Bootwalla, Daniel J. Weisenberger, Shaowu Meng, Mei Huang, Elaine R. Mardis, Gordon Saksena, Nicholas J. Petrelli, Yvonne Owusu-Sarpong, Christopher C. Benz, Bernard Kohl, Jingchun Zhu, David I. Heiman, Carol Farver, Scot Waring, Richard A. Moore, Darshan Singh, Andrew D. Cherniack, Rameen Beroukhim, Michael S. Lawrence, Xiaojia Ren, Marc Ladanyi, Stacey Gabriel, Christine Czerwinski, Alan P. Hoyle, Cancer Genome Atlas Research Network, Collisson, E. A., Campbell, J.D., Brooks, A.N., Berger, A.H., Lee, W., Chmielecki, J., Beer, D.G., Cope, L., Creighton, C.J., Danilova, L., Ding, L., Getz, G., Hammerman, P.S., Hayes, D.N., Hernandez, B., Herman, J.G., Heymach, J.V., Jurisica, I., Kucherlapati, R., Kwiatkowski, D., Ladanyi, M., Robertson, G., Schultz, N., Shen, R., Sinha, R., Sougnez, C., Tsao, M.S., Travis, W.D., Weinstein, J.N., Wigle, D.A., Wilkerson, M.D., Chu, A., Cherniack, A.D., Hadjipanayis, A., Rosenberg, M., Weisenberger, D.J., Laird, P.W., Radenbaugh, A., Ma, S., Stuart, J.M., Averett Byers, L., Baylin, S.B., Govindan, R., Meyerson, M., Gabriel, S.B., Cibulskis, K., Kim, J., Stewart, C., Lichtenstein, L., Lander, E.S., Lawrence, M.S., Kandoth, C., Fulton, R., Fulton, L.L., McLellan, M.D., Wilson, R.K., Ye, K., Fronick, C.C., Maher, C.A., Miller, C.A., Wendl, M.C., Cabanski, C., Mardis, E., Wheeler, D., Balasundaram, M., Butterfield, Y.S., Carlsen, R., Chuah, E., Dhalla, N., Guin, R., Hirst, C., Lee, D., Li, H.I., Mayo, M., Moore, R.A., Mungall, A.J., Schein, J.E., Sipahimalani, P., Tam, A., Varhol, R., Robertson, A., Wye, N., Thiessen, N., Holt, R.A., Jones, S.J., Marra, M.A., Imielinski, M., Onofrio, R.C., Hodis, E., Zack, T., Helman, E., Sekhar Pedamallu, C., Mesirov, J., Saksena, G., Schumacher, S.E., Carter, S.L., Garraway, L., Beroukhim, R., Lee, S., Mahadeshwar, H.S., Pantazi, A., Protopopov, A., Ren, X., Seth, S., Song, X., Tang, J., Yang, L., Zhang, J., Chen, P.C., Parfenov, M., Wei Xu, A., Santoso, N., Chin, L., Park, P.J., Hoadley, K.A., Auman, J.T., Meng, S., Shi, Y., Buda, E., Waring, S., Veluvolu, U., Tan, D., Mieczkowski, P.A., Jones, C.D., Simons, J.V., Soloway, M.G., Bodenheimer, T., Jefferys, S.R., Roach, J., Hoyle, A.P., Wu, J., Balu, S., Singh, D., Prins, J.F., Marron, J.S., Parker, J.S., Perou, C.M., Liu, J., Maglinte, D.T., Lai, P.H., Bootwalla, M.S., Van Den Berg, D.J., Triche, T., Cho, J., DiCara, D., Heiman, D., Lin, P., Mallard, W., Voet, D., Zhang, H., Zou, L., Noble, M.S., Gehlenborg, N., Thorvaldsdottir, H., Nazaire, M.D., Robinson, J., Aksoy, B.A., Ciriello, G., Taylor, B.S., Dresdner, G., Gao, J., Gross, B., Seshan, V.E., Reva, B., Sumer, S.O., Weinhold, N., Sander, C., Ng, S., Zhu, J., Benz, C.C., Yau, C., Haussler, D., Spellman, P.T., Kimes, P.K., Broom, B.M., Wang, J., Lu, Y., Kwok Shing Ng, P., Diao, L., Liu, W., Amos, C.I., Akbani, R., Mills, G.B., Curley, E., Paulauskis, J., Lau, K., Morris, S., Shelton, T., Mallery, D., Gardner, J., Penny, R., Saller, C., Tarvin, K., Richards, W.G., Cerfolio, R., Bryant, A., Raymond, D.P., Pennell, N.A., Farver, C., Czerwinski, C., Huelsenbeck-Dill, L., Iacocca, M., Petrelli, N., Rabeno, B., Brown, J., Bauer, T., Dolzhanskiy, O., Potapova, O., Rotin, D., Voronina, O., Nemirovich-Danchenko, E., Fedosenko, K.V., Gal, A., Behera, M., Ramalingam, S.S., Sica, G., Flieder, D., Boyd, J., Weaver, J., Kohl, B., Huy Quoc Thinh, D., Sandusky, G., Juhl, H., Duhig, E., Illei, P., Gabrielson, E., Shin, J., Lee, B., Rodgers, K., Trusty, D., Brock, M.V., Williamson, C., Burks, E., Rieger-Christ, K., Holway, A., Sullivan, T., Asiedu, M.K., Kosari, F., Rekhtman, N., Zakowski, M., Rusch, V.W., Zippile, P., Suh, J., Pass, H., Goparaju, C., Owusu-Sarpong, Y., Bartlett, J.M., Kodeeswaran, S., Parfitt, J., Sekhon, H., Albert, M., Eckman, J., Myers, J.B., Cheney, R., Morrison, C., Gaudioso, C., Borgia, J.A., Bonomi, P., Pool, M., Liptay, M.J., Moiseenko, F., Zaytseva, I., Dienemann, H., Meister, M., Schnabel, P.A., Muley, T.R., Peifer, M., Gomez-Fernandez, C., Herbert, L., Egea, S., Huang, M., Thorne, L.B., Boice, L., Hill Salazar, A., Funkhouser, W.K., Rathmell, W.K., Dhir, R., Yousem, S.A., Dacic, S., Schneider, F., Siegfried, J.M., Hajek, R., Watson, M.A., McDonald, S., Meyers, B., Clarke, B., Yang, I.A., Fong, K.M., Hunter, L., Windsor, M., Bowman, R.V., Peters, S., Letovanec, I., Khan, K.Z., Jensen, M.A., Snyder, E.E., Srinivasan, D., Kahn, A.B., Baboud, J., Pot, D.A., Mills Shaw, K.R., Sheth, M., Davidsen, T., Demchok, J.A., Wang, Z., Tarnuzzer, R., Zenklusen, J.C., Ozenberger, B.A., Sofia, H.J., Massachusetts Institute of Technology. Department of Biology, and Lander, Eric S.

Subjects
Male, Lung Neoplasms, Adenocarcinoma/genetics, Adenocarcinoma/pathology, Cell Cycle Proteins/genetics, Female, Gene Dosage, Gene Expression Regulation, Neoplastic, Genomics, Humans, Lung Neoplasms/genetics, Lung Neoplasms/pathology, Molecular Typing, Mutation/genetics, Oncogenes/genetics, Sex Factors, Transcriptome/genetics, Adenocarcinoma of Lung, Cell Cycle Proteins, Biology, Adenocarcinoma, Exon, Germline mutation, microRNA, Adenocarcinoma of the lung, medicine, Gene, Multidisciplinary, Oncogene, Oncogenes, medicine.disease, MET Exon 14 Skipping Mutation, Molecular biology, 3. Good health, Mutation, Transcriptome
Abstract

Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis.

Published
2013

14. Evaluation of the Chemical Stability, Membrane Permeability and Antiproliferative Activity of Cyclic Diarylheptanoids from European Hornbeam ( Carpinus betulus L.).

Author

Felegyi-Tóth CA, Heilmann T, Buda E, Stipsicz B, Simon A, Boldizsár I, Bősze S, Riethmüller E, and Alberti Á

Subjects
Humans, Animals, Cell Membrane Permeability, Biological Assay, Blood-Brain Barrier, Diarylheptanoids pharmacology, Betulaceae, Lepidoptera
Abstract

Four cyclic diarylheptanoids-carpinontriols A ( 1 ) and B ( 2 ), giffonin X ( 3 ) and 3,12,17-trihydroxytricyclo [12.3.1.1 2,6 ]nonadeca-1(18),2(19),3,5,14,16-hexaene-8,11-dione ( 4 )-were isolated from Carpinus betulus (Betulaceae). Chemical stability of the isolated diarylheptanoids was evaluated as a function of storage temperature (-15, 5, 22 °C) and time (12 and 23 weeks). The effect of the solvent and the pH (1.2, 6.8, 7.4) on the stability of these diarylheptanoids was also investigated. Compounds 2 and 4 showed good stability both in aqueous and methanolic solutions at all investigated temperatures. Only 2 was stable at all three studied biorelevant pH values. Degradation products of 1 and 3 were formed by the elimination of a water molecule from the parent compounds, as confirmed by ultrahigh-performance liquid chromatography-high-resolution tandem mass spectrometry (UHPLC-HR-MS). The permeability of the compounds across biological membranes was evaluated by the parallel artificial membrane permeability assay (PAMPA). Compound 3 possesses a log Pe value of -5.92 ± 0.04 in the blood-brain barrier-specific PAMPA-BBB study, indicating that it may be able to cross the blood-brain barrier via passive diffusion. The in vitro antiproliferative activity of the compounds was investigated against five human cancer cell lines, confirming that 1 inhibits cell proliferation in A2058 human metastatic melanoma cells.

Published
2023
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15. Land value dynamics and the spatial evolution of cities following COVID 19 using big data analytics.

Author

Buda E, Broitman D, and Czamanski D

Abstract

In this paper, we present results of a land-use forecasting model that we calibrated with vast geo-referenced data of a major metropolitan area. Each land parcel includes information concerning regulations indicating permitted land-uses as well as the certain characteristics of existing buildings. Data concerning all real estate transactions include information about the assets and the price of the exchanges. Based on these data we estimated the spatial dynamics of land values in the metropolitan area over time and identified locations experiencing development pressures. This analysis allows us to forecast plausible futures of the urban spatial configuration. Taking the approach one step further, we propose simulations motivated by the natural experiment of COVID 19. We assumed that part of the behavioral changes observed during the pandemic will endure. The resulting simulations provide forecasts of the future spatial structure of the metropolitan area. Comparing the actual and the forecasted scenarios we interpret the spatial dynamics of the city as they would be if a business-as-usual-pre-Covid-19 scenario is realized, and possible trend changes if the impact of the pandemic is long lasting., Competing Interests: Conflicts of interestNot applicable., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022.)

Published
2023
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17. Scaling of gill metabolic potential as a function of salinity in the euryhaline crab, Callinectes sapidus rathbun.

Author

Kinsey ST, Buda E, and Nordeen J

Subjects
Adaptation, Physiological drug effects, Animals, Body Constitution, Body Weight, Brachyura anatomy & histology, Brachyura metabolism, Gills anatomy & histology, Gills metabolism, Organ Size, Brachyura drug effects, Brachyura enzymology, Energy Metabolism drug effects, Gills drug effects, Gills enzymology, Sodium Chloride pharmacology, Water chemistry
Abstract

The body-size scaling pattern of enzymes that are important in energy metabolism was examined in gills of the blue crab as a function of acclimation salinity. We hypothesized that the higher surface-area-to-volume ratio of small crabs would impose a greater metabolic cost for hyperosmoregulation, leading to an increase in the capacity for ATP production in gills. Postmetamorphic crabs spanning a 2,500-fold range in body mass were examined following a 7-d exposure to a salinity of 35, 17, or 5 ppt. The posterior gills, which are the principal site of osmoregulatory ion pumping, generally had higher activities than the anterior gills, which are primarily used for gas exchange, and this discrepancy was greatest in small crabs. A significant effect of salinity was found only for the enzyme citrate synthase, where the activity was highest at the lowest salinity. Although most enzymes scaled negatively with body mass, the activity was independent of size over a 250-fold size range that encompassed the body masses of juvenile crabs but decreased abruptly in the adult crabs. These data suggest that ion pumping associated with osmoregulation may represent a greater energetic challenge in smaller crabs, and this is reflected in the relatively higher metabolic potential of the posterior gills. However, acclimation to different salinity regimes does not lead to dramatic global changes in the capacity for energy metabolism.

Published
2003
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18. A new class of drugs that inhibit platelet release and aggregation.

Author

Shulman NR, Pollard HB, Tack-Goldman K, and Buda E

Subjects
Anions metabolism, Biological Transport drug effects, Exocytosis drug effects, Furosemide pharmacology, Hydrogen-Ion Concentration, Osmolar Concentration, Probenecid pharmacology, Pyridoxal Phosphate pharmacology, Sulfinpyrazone pharmacology, Suramin pharmacology, Thrombin metabolism, Blood Platelets metabolism, Platelet Aggregation drug effects, Serotonin metabolism
Published
1978

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