Integrated genomic analyses of ovarian carcinoma.
Bell, D. 1; Berchuck, A. 2,3; Birrer, M. 4,5; Chien, J. 6; Cramer, D. W. 7; Dao, F. 8; Dhir, R. 9; DiSaia, P. 10; Gabra, H. 11; Glenn, P. 12; Godwin, A. K. 13; Gross, J. 14; Hartmann, L. 15; Huang, M. 16; Huntsman, D. G. 17; Iacocca, M. 18; Imielinski, M. 5; Kalloger, S. 17; Karlan, B. Y. 14,19; Morrison, C. 22,23; Mutch, D. 24; Olvera, N. 8; Orsulic, S. 14; Park, K. 25; Petrelli, N. 26; Rabeno, B. 18; Rader, J. S. 27; Sikic, B. I. 28; Smith-McCune, K. 12; Sood, A. K. 29,30; Bowtell, D. 31; Testa, J. R. 33; Genome sequencing centres: Baylor College of Medicine; Chang, K. 34; Dinh, H. H. 34; Drummond, J. A. 34; Fowler, G. 34; Gunaratne, P. 34; Hawes, A. C. 34; Kovar, C. L. 34; Lewis, L. R. 34; Morgan, M. B. 34; Newsham, I. F. 34; Santibanez, J. 34; Reid, J. G. 34; Trevino, L. R. 34; Wu, Y.-Q. 34; Wang, M. 34; Muzny, D. M. 34; Wheeler, D. A. 34; Gibbs, R. A. 34; Broad Institute; Sivachenko, A. Y. 35; Sougnez, C. 37; Wilkinson, J. 38; Bloom, T. 39; Fennell, T. 40; Baldwin, J. 38; Gabriel, S. 41; Lander, E. S. 35,42,43; Washington University in St Louis; Ding, L. 44; Fulton, R. S. 44; Koboldt, D. C. 44; McLellan, M. D. 44; Wylie, T. 44; Walker, J. 44; O'Laughlin, M. 44; Dooling, D. J. 44; Fulton, L. 44; Abbott, R. 44; Dees, N. D. 44; Zhang, Q. 44; Kandoth, C. 44; Wendl, M. 44; Schierding, W. 44; Shen, D. 44; Harris, C. C. 44; Schmidt, H. 44; Kalicki, J. 44; Delehaunty, K. D. 44; Fronick, C. C. 44; Demeter, R. 44; Cook, L. 44; Wallis, J. W. 44; Lin, L. 44; Magrini, V. J. 44; Hodges, J. S. 44; Eldred, J. M. 44; Smith, S. M. 44; Pohl, C. S. 44; Vandin, F. 45; Raphael, B. J. 45; Weinstock, G. M. 44; Mardis, E. R. 44; Wilson, R. K. 44; Cancer genome characterization centres: Broad InstituteDana-Farber Cancer Institute /; Meyerson, M. 35,47,48; Winckler, W. 37; Verhaak, R. G. W. 35,47; Carter, S. L. 35,47; Mermel, C. H. 35,47; Nguyen, H. 35; Onofrio, R. C. 35; Hubbard, D. 35,47,48; Gupta, S. 35; Crenshaw, A. 35; Ramos, A. H. 35,47,48; Harvard Medical School; Protopopov, A. 49; Zhang, Juinhua 49; Kim, T. M. 51; Perna, I. 49; Xiao, Y. 49; Ren, G. 49; Sathiamoorthy, N. 52; Lee, E. 51; Park, P. J. 51,53; Kucherlapati, R. 54; HudsonAlpha InstituteStanford University /; Absher, D. M. 55; Waite, L. 55; Sherlock, G. 56; Brooks, J. D. 57; Li, J. Z. 58; Xu, J. 58; Myers, R. M. 55; University of Southern CaliforniaJohns Hopkins University /; Laird, P. W. 59; Cope, L. 60; Herman, J. G. 61; Shen, H. 59; Weisenberger, D. J. 59; Noushmehr, H. 59; Pan, F. 59; Triche, T. Jr 59; Berman, B. P. 59; Van Den Berg, D. J. 59; Buckley, J. 59; Baylin, S. B. 61; Lawrence Berkeley National Laboratory; Jakkula, L. R. 62; Dorton, S. 62; Marr, H. 62; Choi, Y. G. 64; Wang, V. 65; Wang, N. J. 62; Ngai, J. 64; Conboy, J. G. 62; Feiler, H. S. 62; Memorial Sloan-Kettering Cancer Center; Socci, N. D. 67; Liang, Y. 67; Lash, A. E. 67; Brennan, C. 69; Viale, A. 70; University of North Carolina at Chapel Hill; Meng, S. 73; Shi, Y. 73; Li, L. 73; Turman, Y. J. 73; Zang, D. 73; Helms, E. B. 73; Zhou, X. 73; Wu, J. 73; Topal, M. D. 72,73; Genome data analysis centres: Broad Institute; Zhang, Junihua 49; Wu, C. J. 49; Shukla, S. 49; Sivachenko, A. 35; Jing, R. 35; Liu, Y. 49; Noble, M. 35; Johns Hopkins University; Carter, H. 75; Kim, D. 75; Karchin, R. 75; Lawrence Berkeley National Laboratory; Korkola, J. E. 62; Heiser, L. M. 62; Cho, R. J. 62; Hu, Z. 62; Parvin, B. 62; Memorial Sloan-Kettering Cancer Center; Cerami, E. 67; Olshen, A.; Reva, B. 67; Antipin, Y. 67; Shen, R.; Mankoo, P. 67; Sheridan, R. 67; Ciriello, G. 67; Chang, W. K. 67,77; Bernanke, J. A. 78; University of California Santa CruzBuck Institute /; Haussler, D. 79,80; Benz, C. C. 81; Stuart, J. M. 79; Benz, S. C. 79; Sanborn, J. Z. 79; Vaske, C. J. 79,82; Zhu, J. 79; Szeto, C. 79; Scott, G. K. 81; Yau, C. 81; University of North Carolina at Chapel Hill; Wilkerson, M. D. 73; The University of Texas MD Anderson Cancer Center; Zhang, N. 83; Akbani, R. 83; Baggerly, K. A. 83; Yung, W. K. 84; Weinstein, J. N. 20,83; Biospecimen core resource; Shelton, T. 32; Grimm, D. 32; Hatfield, M. 32; Morris, S. 32; Yena, P. 32; Rhodes, P. 32; Sherman, M. 32; Paulauskis, J. 32; Millis, S. 32; Data coordination centre; Kahn, A. 85; Greene, J. M. 85; Sfeir, R. 85; Jensen, M. A. 85; Chen, J. 85; Whitmore, J. 85; Alonso, S. 85; Jordan, J. 85; Chu, A. 85; Zhang, Jinghui 86; Project teams: National Cancer Institute; Barker, A.; Compton, C.; Eley, G.; Ferguson, M. 88; Fielding, P.; Gerhard, D. S.; Myles, R.; Schaefer, C.; Mills Shaw, K. R.; Vaught, J.; Vockley, J. B.; National Human Genome Research Institute; Good, P. J. 89; Guyer, M. S. 89; Ozenberger, B. 89; Peterson, J. 89; Thomson, E. 89
[Article]
Nature.
474(7353):609-615, June 30, 2011.
(Format: HTML, PDF)
: A catalogue of molecular aberrations that cause ovarian cancer is critical for developing and deploying therapies that will improve patients' lives. The Cancer Genome Atlas project has analysed messenger RNA expression, microRNA expression, promoter methylation and DNA copy number in 489 high-grade serous ovarian adenocarcinomas and the DNA sequences of exons from coding genes in 316 of these tumours. Here we report that high-grade serous ovarian cancer is characterized by TP53 mutations in almost all tumours (96%); low prevalence but statistically recurrent somatic mutations in nine further genes including NF1, BRCA1, BRCA2, RB1 and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes. Analyses delineated four ovarian cancer transcriptional subtypes, three microRNA subtypes, four promoter methylation subtypes and a transcriptional signature associated with survival duration, and shed new light on the impact that tumours with BRCA1/2 (BRCA1 or BRCA2) and CCNE1 aberrations have on survival. Pathway analyses suggested that homologous recombination is defective in about half of the tumours analysed, and that NOTCH and FOXM1 signalling are involved in serous ovarian cancer pathophysiology.
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