Integrated genomic analyses of ovarian carcinoma
Author(s)
Bell, D; Berchuck, A; Birrer, M; Chien, J; Cramer, DW; Dao, F; Dhir, R; DiSaia, P; Gabra, H; Glenn, P; Godwin, AK; Gross, J; Hartmann, L; Huang, M; Huntsman, DG; Iacocca, M; Imielinski, M; Kalloger, S; Karlan, BY; Mills, GB; Morrison, C; Mutch, D; Olvera, N; Orsulic, S; Park, K; Petrelli, N; Rabeno, B; Rader, JS; Sikic, BI; Smith-McCune, K; Sood, AK; Bowtell, D; Penny, R; Testa, JR; Chang, K; Dinh, HH; Drummond, JA; Fowler, G; Gunaratne, P; Hawes, AC; Kovar, CL; Lewis, LR; Morgan, MB; Newsham, IF; Santibanez, J; Reid, JG; Trevino, LR; Wu, YQ; Wang, M; Muzny, DM; Wheeler, DA; Gibbs, RA; Cibulskis, K; Sivachenko, AY; Sougnez, C; Voet, D; Wilkinson, J; Bloom, T; Fennell, T; Baldwin, J; Gabriel, S; Lander, ES; Ding, L; Fulton, RS; Koboldt, DC; McLellan, MD; Wylie, T; Walker, J; O'Laughlin, M; Dooling, DJ; Fulton, L; Abbott, R; Dees, ND; Zhang, Q; Kandoth, C; Wendl, M; Schierding, W; Shen, D; Harris, CC; Schmidt, H; Kalicki, J; Delehaunty, KD; Fronick, CC; Demeter, R; Cook, L; Wallis, JW; Lin, L; Magrini, VJ; Hodges, JS; Eldred, JM; Smith, SM; Pohl, CS; Vandin, F; Raphael, BJ; Weinstock, GM; Mardis, R; Wilson, RK; Meyerson, M; Winckler, W; Getz, G; Verhaak, RGW; Carter, SL; Mermel, CH; Nguyen, H; Onofrio, RC; Hubbard, D; Gupta, S; Crenshaw, A; Ramos, AH; Ardlie, K; Chin, L; Protopopov, A; Kim, TM; Perna, I; Xiao, Y; Zhang, H; Ren, G; Sathiamoorthy, N; Lee, E; Park, PJ; Kucherlapati, R; Absher, DM; Waite, L; Sherlock, G; Brooks, JD; Li, JZ; Xu, J; Myers, RM; Laird, PW; Cope, L; Herman, JG; Shen, H; Weisenberger, DJ; Noushmehr, H; Pan, F; Triche, T; Berman, BP; Van den Berg, DJ; Buckley, J; Baylin, SB; Spellman, PT; Purdom, E; Neuvial, P; Jakkula, LR; Dorton, S; Marr, H; Choi, YG; Wang, V; Wang, NJ; Ngai, J; Conboy, JG; Feiler, HS; Speed, TP; Socci, ND; Liang, Y; Taylor, BS; Schultz, N; Borsu, L; Lash, AE; Brennan, C; Viale, A; Ladanyi, M; Meng, S; Shi, Y; Li, L; Turman, YJ; Zang, D; Helms, EB; Balu, S; Zhou, X; Wu, J; Topal, MD; Perou, CM; Saksena, G; Zhang, JNH; Wu, CJ; Shukla, S; Lawrence, MS; Sivachenko, A; Jing, R; Park, RW; Liu, Y; Noble, M; Carter, H; Kim, D; Karchin, R; Bengtsson, H; Durinck, S; Han, J; Korkola, JE; Heiser, LM; Cho, RJ; Hu, Z; Parvin, B; Gray, JW; Cerami, E; Olshen, A; Reva, B; Antipin, Y; Shen, R; Mankoo, P; Sheridan, R; Ciriello, G; Chang, WK; Bernanke, JA; Levine, DA; Sander, C; Haussler, D; Benz, CC; Stuart, JM; Benz, SC; Sanborn, JZ; Vaske, CJ; Zhu, J; Szeto, C; Scott, GK; Yau, C; Hoadley, KA; Du, Y; Hayes, DN; Wilkerson, MD; Zhang, N; Akbani, R; Baggerly, KA; Yung, WK; Weinstein, JN; Shelton, T; Grimm, D; Hatfield, M; Morris, S; Yena, P; Rhodes, P; Sherman, M; Paulauskis, J; Millis, S; Kahn, A; Greene, JM; Sfeir, R; Jensen, MA; Chen, J; Whitmore, J; Alonso, S; Jordan, J; Chu, A; Zhang, JH; Barker, A; Compton, C; Eley, G; Ferguson, M; Fielding, P; Gerhard, DS; Myles, R; Schaefer, C; Shaw, KRM; Vaught, J; Vockley, JB; Good, PJ; Guyer, MS; Ozenberger, B; Peterson, J; Thomson, E;
Details
Publication Year 2011-06-30, Volume 474, Issue #7353, Page 609-615
Journal Title
NATURE
Publication Type
Journal Article
Abstract
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.
Publisher
NATURE PUBLISHING GROUP
Keywords
HIGH-THROUGHPUT ANNOTATION; GYNECOLOGIC-ONCOLOGY-GROUP; GRADE SEROUS CARCINOMA; BRCA MUTATION CARRIERS; CLEAR-CELL CARCINOMA; SOMATIC MUTATIONS; CANCER STATISTICS; DRIVER MUTATIONS; HYBRID SELECTION; MUTANT-CELLS
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2011-06-30 12:00:00
Last Modified: 0001-01-01 12:00:00
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