Integrated genomic analyses of ovarian carcinoma

D. Bell, A. Berchuck, M. Birrer, J. Chien, D. W. Cramer, F. Dao, R. Dhir, P. Disaia, H. Gabra, P. Glenn, A. K. Godwin, J. Gross, L. Hartmann, M. Huang, D. G. Huntsman, M. Iacocca, M. Imielinski, S. Kalloger, B. Y. Karlan, D. A. LevineGordon Mills, C. Morrison, D. Mutch, N. Olvera, S. Orsulic, K. Park, N. Petrelli, B. Rabeno, J. S. Rader, B. I. Sikic, K. Smith-Mccune, A. K. Sood, D. Bowtell, R. Penny, J. R. Testa, K. Chang, H. H. Dinh, J. A. Drummond, G. Fowler, P. Gunaratne, A. C. Hawes, C. L. Kovar, L. R. Lewis, M. B. Morgan, I. F. Newsham, J. Santibanez, J. G. Reid, L. R. Trevino, Y. Q. Wu, M. Wang, D. M. Muzny, D. A. Wheeler, R. A. Gibbs, G. Getz, M. S. Lawrence, K. Cibulskis, A. Y. Sivachenko, C. Sougnez, D. Voet, J. Wilkinson, T. Bloom, K. Ardlie, T. Fennell, J. Baldwin, S. Gabriel, E. S. Lander, L. Ding, R. S. Fulton, D. C. Koboldt, M. D. McLellan, T. Wylie, J. Walker, M. O'Laughlin, D. J. Dooling, L. Fulton, R. Abbott, N. D. Dees, Q. Zhang, C. Kandoth, M. Wendl, W. Schierding, D. Shen, C. C. Harris, H. Schmidt, J. Kalicki, K. D. Delehaunty, C. C. Fronick, R. Demeter, L. Cook, J. W. Wallis, L. Lin, V. J. Magrini, J. S. Hodges, J. M. Eldred, S. M. Smith, C. S. Pohl, F. Vandin, B. J. Raphael, G. M. Weinstock, E. R. Mardis, R. K. Wilson, M. Meyerson, W. Winckler, G. Getz, R. G W Verhaak, S. L. Carter, C. H. Mermel, G. Saksena, H. Nguyen, R. C. Onofrio, M. S. Lawrence, D. Hubbard, S. Gupta, A. Crenshaw, A. H. Ramos, K. Ardlie, L. Chin, A. Protopopov, Juinhua Zhang, T. M. Kim, I. Perna, Y. Xiao, H. Zhang, G. Ren, N. Sathiamoorthy, R. W. Park, E. Lee, P. J. Park, R. Kucherlapati, D. M. Absher, L. Waite, G. Sherlock, J. D. Brooks, J. Z. Li, J. Xu, R. M. Myers, P. W. Laird, L. Cope, J. G. Herman, H. Shen, D. J. Weisenberger, H. Noushmehr, F. Pan, T. Triche, B. P. Berman, Paul Spellman, J. Buckley, S. B. Baylin, P. T. Spellman, E. Purdom, P. Neuvial, H. Bengtsson, L. R. Jakkula, S. Durinck, J. Han, S. Dorton, H. Marr, Y. G. Choi, V. Wang, N. J. Wang, Heidi Feiler, J. G. Conboy, Joe Gray, H. S. Feiler, T. P. Speed, J. W. Gray, D. A. Levine, N. D. Socci, Y. Liang, B. S. Taylor, N. Schultz, L. Borsu, A. E. Lash, C. Brennan, A. Viale, C. Sander, M. Ladanyi, K. A. Hoadley, S. Meng, Y. Du, Y. Shi, L. Li, Y. J. Turman, D. Zang, E. B. Helms, S. Balu, X. Zhou, J. Wu, M. D. Topal, D. N. Hayes, C. M. Perou, G. Getz, D. Voet, G. Saksena, Junihua Zhang, H. Zhang, James Korkola, Laura Heiser, K. Cibulskis, Zhi Hu, A. Sivachenko, R. Jing, R. W. Park, Y. Liu, P. J. Park, M. Noble, L. Chin, H. Carter, D. Kim, R. Karchin, P. T. Spellman, E. Purdom, P. Neuvial, H. Bengtsson, S. Durinck, J. Han, J. E. Korkola, L. M. Heiser, R. J. Cho, Z. Hu, B. Parvin, T. P. Speed, J. W. Gray, N. Schultz, E. Cerami, B. S. Taylor, A. Olshen, B. Reva, Y. Antipin, R. Shen, P. Mankoo, R. Sheridan, G. Ciriello, W. K. Chang, J. A. Bernanke, L. Borsu, D. A. Levine, M. Ladanyi, C. Sander, D. Haussler, C. C. Benz, J. M. Stuart, S. C. Benz, J. Z. Sanborn, C. J. Vaske, J. Zhu, C. Szeto, G. K. Scott, C. Yau, K. A. Hoadley, Y. Du, S. Balu, D. N. Hayes, C. M. Perou, M. D. Wilkerson, N. Zhang, R. Akbani, K. A. Baggerly, W. K. Yung, G. B. Mills, J. N. Weinstein, R. Penny, T. Shelton, D. Grimm, M. Hatfield, S. Morris, P. Yena, P. Rhodes, M. Sherman, J. Paulauskis, S. Millis, A. Kahn, J. M. Greene, R. Sfeir, M. A. Jensen, J. Chen, J. Whitmore, S. Alonso, J. Jordan, A. Chu, Jinghui Zhang, A. Barker, C. Compton, G. Eley, M. Ferguson, P. Fielding, D. S. Gerhard, R. Myles, C. Schaefer, K. R. Mills Shaw, J. Vaught, J. B. Vockley, P. J. Good, M. S. Guyer, B. Ozenberger, J. Peterson, E. Thomson

Research output: Contribution to journalArticle

3666 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)609-615
Number of pages7
JournalNature
Volume474
Issue number7353
DOIs
StatePublished - Jun 30 2011
Externally publishedYes

Fingerprint

Ovarian Neoplasms
Carcinoma
Neoplasms
MicroRNAs
Methylation
Genes
Mutation
Survival
Atlases
Homologous Recombination
DNA Methylation
Exons
Adenocarcinoma
Genome
Messenger RNA
DNA
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Bell, D., Berchuck, A., Birrer, M., Chien, J., Cramer, D. W., Dao, F., ... Thomson, E. (2011). Integrated genomic analyses of ovarian carcinoma. Nature, 474(7353), 609-615. https://doi.org/10.1038/nature10166

Integrated genomic analyses of ovarian carcinoma. / Bell, D.; Berchuck, A.; Birrer, M.; Chien, J.; Cramer, D. W.; Dao, F.; Dhir, R.; Disaia, P.; Gabra, H.; Glenn, P.; Godwin, A. K.; Gross, J.; Hartmann, L.; Huang, M.; Huntsman, D. G.; Iacocca, M.; Imielinski, M.; Kalloger, S.; Karlan, B. Y.; Levine, D. A.; Mills, Gordon; Morrison, C.; Mutch, D.; Olvera, N.; Orsulic, S.; Park, K.; Petrelli, N.; Rabeno, B.; Rader, J. S.; Sikic, B. I.; Smith-Mccune, K.; Sood, A. K.; Bowtell, D.; Penny, R.; Testa, J. R.; Chang, K.; Dinh, H. H.; Drummond, J. A.; Fowler, G.; Gunaratne, P.; Hawes, A. C.; Kovar, C. L.; Lewis, L. R.; Morgan, M. B.; Newsham, I. F.; Santibanez, J.; Reid, J. G.; Trevino, L. R.; Wu, Y. Q.; Wang, M.; Muzny, D. M.; Wheeler, D. A.; Gibbs, R. A.; Getz, G.; Lawrence, M. S.; Cibulskis, K.; Sivachenko, A. Y.; Sougnez, C.; Voet, D.; Wilkinson, J.; Bloom, T.; Ardlie, K.; Fennell, T.; Baldwin, J.; Gabriel, S.; Lander, E. S.; Ding, L.; Fulton, R. S.; Koboldt, D. C.; McLellan, M. D.; Wylie, T.; Walker, J.; O'Laughlin, M.; Dooling, D. J.; Fulton, L.; Abbott, R.; Dees, N. D.; Zhang, Q.; Kandoth, C.; Wendl, M.; Schierding, W.; Shen, D.; Harris, C. C.; Schmidt, H.; Kalicki, J.; Delehaunty, K. D.; Fronick, C. C.; Demeter, R.; Cook, L.; Wallis, J. W.; Lin, L.; Magrini, V. J.; Hodges, J. S.; Eldred, J. M.; Smith, S. M.; Pohl, C. S.; Vandin, F.; Raphael, B. J.; Weinstock, G. M.; Mardis, E. R.; Wilson, R. K.; Meyerson, M.; Winckler, W.; Getz, G.; Verhaak, R. G W; Carter, S. L.; Mermel, C. H.; Saksena, G.; Nguyen, H.; Onofrio, R. C.; Lawrence, M. S.; Hubbard, D.; Gupta, S.; Crenshaw, A.; Ramos, A. H.; Ardlie, K.; Chin, L.; Protopopov, A.; Zhang, Juinhua; Kim, T. M.; Perna, I.; Xiao, Y.; Zhang, H.; Ren, G.; Sathiamoorthy, N.; Park, R. W.; Lee, E.; Park, P. J.; Kucherlapati, R.; Absher, D. M.; Waite, L.; Sherlock, G.; Brooks, J. D.; Li, J. Z.; Xu, J.; Myers, R. M.; Laird, P. W.; Cope, L.; Herman, J. G.; Shen, H.; Weisenberger, D. J.; Noushmehr, H.; Pan, F.; Triche, T.; Berman, B. P.; Spellman, Paul; Buckley, J.; Baylin, S. B.; Spellman, P. T.; Purdom, E.; Neuvial, P.; Bengtsson, H.; Jakkula, L. R.; Durinck, S.; Han, J.; Dorton, S.; Marr, H.; Choi, Y. G.; Wang, V.; Wang, N. J.; Feiler, Heidi; Conboy, J. G.; Gray, Joe; Feiler, H. S.; Speed, T. P.; Gray, J. W.; Levine, D. A.; Socci, N. D.; Liang, Y.; Taylor, B. S.; Schultz, N.; Borsu, L.; Lash, A. E.; Brennan, C.; Viale, A.; Sander, C.; Ladanyi, M.; Hoadley, K. A.; Meng, S.; Du, Y.; Shi, Y.; Li, L.; Turman, Y. J.; Zang, D.; Helms, E. B.; Balu, S.; Zhou, X.; Wu, J.; Topal, M. D.; Hayes, D. N.; Perou, C. M.; Getz, G.; Voet, D.; Saksena, G.; Zhang, Junihua; Zhang, H.; Korkola, James; Heiser, Laura; Cibulskis, K.; Hu, Zhi; Sivachenko, A.; Jing, R.; Park, R. W.; Liu, Y.; Park, P. J.; Noble, M.; Chin, L.; Carter, H.; Kim, D.; Karchin, R.; Spellman, P. T.; Purdom, E.; Neuvial, P.; Bengtsson, H.; Durinck, S.; Han, J.; Korkola, J. E.; Heiser, L. M.; Cho, R. J.; Hu, Z.; Parvin, B.; Speed, T. P.; Gray, J. W.; Schultz, N.; Cerami, E.; Taylor, B. S.; Olshen, A.; Reva, B.; Antipin, Y.; Shen, R.; Mankoo, P.; Sheridan, R.; Ciriello, G.; Chang, W. K.; Bernanke, J. A.; Borsu, L.; Levine, D. A.; Ladanyi, M.; Sander, C.; Haussler, D.; Benz, C. C.; Stuart, J. M.; Benz, S. C.; Sanborn, J. Z.; Vaske, C. J.; Zhu, J.; Szeto, C.; Scott, G. K.; Yau, C.; Hoadley, K. A.; Du, Y.; Balu, S.; Hayes, D. N.; Perou, C. M.; Wilkerson, M. D.; Zhang, N.; Akbani, R.; Baggerly, K. A.; Yung, W. K.; Mills, G. B.; Weinstein, J. N.; Penny, R.; Shelton, T.; Grimm, D.; Hatfield, M.; Morris, S.; Yena, P.; Rhodes, P.; Sherman, M.; Paulauskis, J.; Millis, S.; Kahn, A.; Greene, J. M.; Sfeir, R.; Jensen, M. A.; Chen, J.; Whitmore, J.; Alonso, S.; Jordan, J.; Chu, A.; Zhang, Jinghui; Barker, A.; Compton, C.; Eley, G.; Ferguson, M.; Fielding, P.; Gerhard, D. S.; Myles, R.; Schaefer, C.; Mills Shaw, K. R.; Vaught, J.; Vockley, J. B.; Good, P. J.; Guyer, M. S.; Ozenberger, B.; Peterson, J.; Thomson, E.

In: Nature, Vol. 474, No. 7353, 30.06.2011, p. 609-615.

Research output: Contribution to journalArticle

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, Levine, DA, Mills, G, 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, Getz, G, Lawrence, MS, Cibulskis, K, Sivachenko, AY, Sougnez, C, Voet, D, Wilkinson, J, Bloom, T, Ardlie, K, 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, ER, Wilson, RK, Meyerson, M, Winckler, W, Getz, G, Verhaak, RGW, Carter, SL, Mermel, CH, Saksena, G, Nguyen, H, Onofrio, RC, Lawrence, MS, Hubbard, D, Gupta, S, Crenshaw, A, Ramos, AH, Ardlie, K, Chin, L, Protopopov, A, Zhang, J, Kim, TM, Perna, I, Xiao, Y, Zhang, H, Ren, G, Sathiamoorthy, N, Park, RW, 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, Spellman, P, Buckley, J, Baylin, SB, Spellman, PT, Purdom, E, Neuvial, P, Bengtsson, H, Jakkula, LR, Durinck, S, Han, J, Dorton, S, Marr, H, Choi, YG, Wang, V, Wang, NJ, Feiler, H, Conboy, JG, Gray, J, Feiler, HS, Speed, TP, Gray, JW, Levine, DA, Socci, ND, Liang, Y, Taylor, BS, Schultz, N, Borsu, L, Lash, AE, Brennan, C, Viale, A, Sander, C, Ladanyi, M, Hoadley, KA, Meng, S, Du, Y, Shi, Y, Li, L, Turman, YJ, Zang, D, Helms, EB, Balu, S, Zhou, X, Wu, J, Topal, MD, Hayes, DN, Perou, CM, Getz, G, Voet, D, Saksena, G, Zhang, J, Zhang, H, Korkola, J, Heiser, L, Cibulskis, K, Hu, Z, Sivachenko, A, Jing, R, Park, RW, Liu, Y, Park, PJ, Noble, M, Chin, L, Carter, H, Kim, D, Karchin, R, Spellman, PT, Purdom, E, Neuvial, P, Bengtsson, H, Durinck, S, Han, J, Korkola, JE, Heiser, LM, Cho, RJ, Hu, Z, Parvin, B, Speed, TP, Gray, JW, Schultz, N, Cerami, E, Taylor, BS, Olshen, A, Reva, B, Antipin, Y, Shen, R, Mankoo, P, Sheridan, R, Ciriello, G, Chang, WK, Bernanke, JA, Borsu, L, Levine, DA, Ladanyi, M, 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, Balu, S, Hayes, DN, Perou, CM, Wilkerson, MD, Zhang, N, Akbani, R, Baggerly, KA, Yung, WK, Mills, GB, Weinstein, JN, Penny, R, 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, J, Barker, A, Compton, C, Eley, G, Ferguson, M, Fielding, P, Gerhard, DS, Myles, R, Schaefer, C, Mills Shaw, KR, Vaught, J, Vockley, JB, Good, PJ, Guyer, MS, Ozenberger, B, Peterson, J & Thomson, E 2011, 'Integrated genomic analyses of ovarian carcinoma', Nature, vol. 474, no. 7353, pp. 609-615. https://doi.org/10.1038/nature10166
Bell D, Berchuck A, Birrer M, Chien J, Cramer DW, Dao F et al. Integrated genomic analyses of ovarian carcinoma. Nature. 2011 Jun 30;474(7353):609-615. https://doi.org/10.1038/nature10166
Bell, D. ; Berchuck, A. ; Birrer, M. ; Chien, J. ; Cramer, D. W. ; Dao, F. ; Dhir, R. ; Disaia, P. ; Gabra, H. ; Glenn, P. ; Godwin, A. K. ; Gross, J. ; Hartmann, L. ; Huang, M. ; Huntsman, D. G. ; Iacocca, M. ; Imielinski, M. ; Kalloger, S. ; Karlan, B. Y. ; Levine, D. A. ; Mills, Gordon ; Morrison, C. ; Mutch, D. ; Olvera, N. ; Orsulic, S. ; Park, K. ; Petrelli, N. ; Rabeno, B. ; Rader, J. S. ; Sikic, B. I. ; Smith-Mccune, K. ; Sood, A. K. ; Bowtell, D. ; Penny, R. ; Testa, J. R. ; Chang, K. ; Dinh, H. H. ; Drummond, J. A. ; Fowler, G. ; Gunaratne, P. ; Hawes, A. C. ; Kovar, C. L. ; Lewis, L. R. ; Morgan, M. B. ; Newsham, I. F. ; Santibanez, J. ; Reid, J. G. ; Trevino, L. R. ; Wu, Y. Q. ; Wang, M. ; Muzny, D. M. ; Wheeler, D. A. ; Gibbs, R. A. ; Getz, G. ; Lawrence, M. S. ; Cibulskis, K. ; Sivachenko, A. Y. ; Sougnez, C. ; Voet, D. ; Wilkinson, J. ; Bloom, T. ; Ardlie, K. ; Fennell, T. ; Baldwin, J. ; Gabriel, S. ; Lander, E. S. ; Ding, L. ; Fulton, R. S. ; Koboldt, D. C. ; McLellan, M. D. ; Wylie, T. ; Walker, J. ; O'Laughlin, M. ; Dooling, D. J. ; Fulton, L. ; Abbott, R. ; Dees, N. D. ; Zhang, Q. ; Kandoth, C. ; Wendl, M. ; Schierding, W. ; Shen, D. ; Harris, C. C. ; Schmidt, H. ; Kalicki, J. ; Delehaunty, K. D. ; Fronick, C. C. ; Demeter, R. ; Cook, L. ; Wallis, J. W. ; Lin, L. ; Magrini, V. J. ; Hodges, J. S. ; Eldred, J. M. ; Smith, S. M. ; Pohl, C. S. ; Vandin, F. ; Raphael, B. J. ; Weinstock, G. M. ; Mardis, E. R. ; Wilson, R. K. ; Meyerson, M. ; Winckler, W. ; Getz, G. ; Verhaak, R. G W ; Carter, S. L. ; Mermel, C. H. ; Saksena, G. ; Nguyen, H. ; Onofrio, R. C. ; Lawrence, M. S. ; Hubbard, D. ; Gupta, S. ; Crenshaw, A. ; Ramos, A. H. ; Ardlie, K. ; Chin, L. ; Protopopov, A. ; Zhang, Juinhua ; Kim, T. M. ; Perna, I. ; Xiao, Y. ; Zhang, H. ; Ren, G. ; Sathiamoorthy, N. ; Park, R. W. ; Lee, E. ; Park, P. J. ; Kucherlapati, R. ; Absher, D. M. ; Waite, L. ; Sherlock, G. ; Brooks, J. D. ; Li, J. Z. ; Xu, J. ; Myers, R. M. ; Laird, P. W. ; Cope, L. ; Herman, J. G. ; Shen, H. ; Weisenberger, D. J. ; Noushmehr, H. ; Pan, F. ; Triche, T. ; Berman, B. P. ; Spellman, Paul ; Buckley, J. ; Baylin, S. B. ; Spellman, P. T. ; Purdom, E. ; Neuvial, P. ; Bengtsson, H. ; Jakkula, L. R. ; Durinck, S. ; Han, J. ; Dorton, S. ; Marr, H. ; Choi, Y. G. ; Wang, V. ; Wang, N. J. ; Feiler, Heidi ; Conboy, J. G. ; Gray, Joe ; Feiler, H. S. ; Speed, T. P. ; Gray, J. W. ; Levine, D. A. ; Socci, N. D. ; Liang, Y. ; Taylor, B. S. ; Schultz, N. ; Borsu, L. ; Lash, A. E. ; Brennan, C. ; Viale, A. ; Sander, C. ; Ladanyi, M. ; Hoadley, K. A. ; Meng, S. ; Du, Y. ; Shi, Y. ; Li, L. ; Turman, Y. J. ; Zang, D. ; Helms, E. B. ; Balu, S. ; Zhou, X. ; Wu, J. ; Topal, M. D. ; Hayes, D. N. ; Perou, C. M. ; Getz, G. ; Voet, D. ; Saksena, G. ; Zhang, Junihua ; Zhang, H. ; Korkola, James ; Heiser, Laura ; Cibulskis, K. ; Hu, Zhi ; Sivachenko, A. ; Jing, R. ; Park, R. W. ; Liu, Y. ; Park, P. J. ; Noble, M. ; Chin, L. ; Carter, H. ; Kim, D. ; Karchin, R. ; Spellman, P. T. ; Purdom, E. ; Neuvial, P. ; Bengtsson, H. ; Durinck, S. ; Han, J. ; Korkola, J. E. ; Heiser, L. M. ; Cho, R. J. ; Hu, Z. ; Parvin, B. ; Speed, T. P. ; Gray, J. W. ; Schultz, N. ; Cerami, E. ; Taylor, B. S. ; Olshen, A. ; Reva, B. ; Antipin, Y. ; Shen, R. ; Mankoo, P. ; Sheridan, R. ; Ciriello, G. ; Chang, W. K. ; Bernanke, J. A. ; Borsu, L. ; Levine, D. A. ; Ladanyi, M. ; Sander, C. ; Haussler, D. ; Benz, C. C. ; Stuart, J. M. ; Benz, S. C. ; Sanborn, J. Z. ; Vaske, C. J. ; Zhu, J. ; Szeto, C. ; Scott, G. K. ; Yau, C. ; Hoadley, K. A. ; Du, Y. ; Balu, S. ; Hayes, D. N. ; Perou, C. M. ; Wilkerson, M. D. ; Zhang, N. ; Akbani, R. ; Baggerly, K. A. ; Yung, W. K. ; Mills, G. B. ; Weinstein, J. N. ; Penny, R. ; Shelton, T. ; Grimm, D. ; Hatfield, M. ; Morris, S. ; Yena, P. ; Rhodes, P. ; Sherman, M. ; Paulauskis, J. ; Millis, S. ; Kahn, A. ; Greene, J. M. ; Sfeir, R. ; Jensen, M. A. ; Chen, J. ; Whitmore, J. ; Alonso, S. ; Jordan, J. ; Chu, A. ; Zhang, Jinghui ; Barker, A. ; Compton, C. ; Eley, G. ; Ferguson, M. ; Fielding, P. ; Gerhard, D. S. ; Myles, R. ; Schaefer, C. ; Mills Shaw, K. R. ; Vaught, J. ; Vockley, J. B. ; Good, P. J. ; Guyer, M. S. ; Ozenberger, B. ; Peterson, J. ; Thomson, E. / Integrated genomic analyses of ovarian carcinoma. In: Nature. 2011 ; Vol. 474, No. 7353. pp. 609-615.
@article{966f35cac1df4262b5a77f5bffe2ac9c,
title = "Integrated genomic analyses of ovarian carcinoma",
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.",
author = "D. Bell and A. Berchuck and M. Birrer and J. Chien and Cramer, {D. W.} and F. Dao and R. Dhir and P. Disaia and H. Gabra and P. Glenn and Godwin, {A. K.} and J. Gross and L. Hartmann and M. Huang and Huntsman, {D. G.} and M. Iacocca and M. Imielinski and S. Kalloger and Karlan, {B. Y.} and Levine, {D. A.} and Gordon Mills and C. Morrison and D. Mutch and N. Olvera and S. Orsulic and K. Park and N. Petrelli and B. Rabeno and Rader, {J. S.} and Sikic, {B. I.} and K. Smith-Mccune and Sood, {A. K.} and D. Bowtell and R. Penny and Testa, {J. R.} and K. Chang and Dinh, {H. H.} and Drummond, {J. A.} and G. Fowler and P. Gunaratne and Hawes, {A. C.} and Kovar, {C. L.} and Lewis, {L. R.} and Morgan, {M. B.} and Newsham, {I. F.} and J. Santibanez and Reid, {J. G.} and Trevino, {L. R.} and Wu, {Y. Q.} and M. Wang and Muzny, {D. M.} and Wheeler, {D. A.} and Gibbs, {R. A.} and G. Getz and Lawrence, {M. S.} and K. Cibulskis and Sivachenko, {A. Y.} and C. Sougnez and D. Voet and J. Wilkinson and T. Bloom and K. Ardlie and T. Fennell and J. Baldwin and S. Gabriel and Lander, {E. S.} and L. Ding and Fulton, {R. S.} and Koboldt, {D. C.} and McLellan, {M. D.} and T. Wylie and J. Walker and M. O'Laughlin and Dooling, {D. J.} and L. Fulton and R. Abbott and Dees, {N. D.} and Q. Zhang and C. Kandoth and M. Wendl and W. Schierding and D. Shen and Harris, {C. C.} and H. Schmidt and J. Kalicki and Delehaunty, {K. D.} and Fronick, {C. C.} and R. Demeter and L. Cook and Wallis, {J. W.} and L. Lin and Magrini, {V. J.} and Hodges, {J. S.} and Eldred, {J. M.} and Smith, {S. M.} and Pohl, {C. S.} and F. Vandin and Raphael, {B. J.} and Weinstock, {G. M.} and Mardis, {E. R.} and Wilson, {R. K.} and M. Meyerson and W. Winckler and G. Getz and Verhaak, {R. G W} and Carter, {S. L.} and Mermel, {C. H.} and G. Saksena and H. Nguyen and Onofrio, {R. C.} and Lawrence, {M. S.} and D. Hubbard and S. Gupta and A. Crenshaw and Ramos, {A. H.} and K. Ardlie and L. Chin and A. Protopopov and Juinhua Zhang and Kim, {T. M.} and I. Perna and Y. Xiao and H. Zhang and G. Ren and N. Sathiamoorthy and Park, {R. W.} and E. Lee and Park, {P. J.} and R. Kucherlapati and Absher, {D. M.} and L. Waite and G. Sherlock and Brooks, {J. D.} and Li, {J. Z.} and J. Xu and Myers, {R. M.} and Laird, {P. W.} and L. Cope and Herman, {J. G.} and H. Shen and Weisenberger, {D. J.} and H. Noushmehr and F. Pan and T. Triche and Berman, {B. P.} and Paul Spellman and J. Buckley and Baylin, {S. B.} and Spellman, {P. T.} and E. Purdom and P. Neuvial and H. Bengtsson and Jakkula, {L. R.} and S. Durinck and J. Han and S. Dorton and H. Marr and Choi, {Y. G.} and V. Wang and Wang, {N. J.} and Heidi Feiler and Conboy, {J. G.} and Joe Gray and Feiler, {H. S.} and Speed, {T. P.} and Gray, {J. W.} and Levine, {D. A.} and Socci, {N. D.} and Y. Liang and Taylor, {B. S.} and N. Schultz and L. Borsu and Lash, {A. E.} and C. Brennan and A. Viale and C. Sander and M. Ladanyi and Hoadley, {K. A.} and S. Meng and Y. Du and Y. Shi and L. Li and Turman, {Y. J.} and D. Zang and Helms, {E. B.} and S. Balu and X. Zhou and J. Wu and Topal, {M. D.} and Hayes, {D. N.} and Perou, {C. M.} and G. Getz and D. Voet and G. Saksena and Junihua Zhang and H. Zhang and James Korkola and Laura Heiser and K. Cibulskis and Zhi Hu and A. Sivachenko and R. Jing and Park, {R. W.} and Y. Liu and Park, {P. J.} and M. Noble and L. Chin and H. Carter and D. Kim and R. Karchin and Spellman, {P. T.} and E. Purdom and P. Neuvial and H. Bengtsson and S. Durinck and J. Han and Korkola, {J. E.} and Heiser, {L. M.} and Cho, {R. J.} and Z. Hu and B. Parvin and Speed, {T. P.} and Gray, {J. W.} and N. Schultz and E. Cerami and Taylor, {B. S.} and A. Olshen and B. Reva and Y. Antipin and R. Shen and P. Mankoo and R. Sheridan and G. Ciriello and Chang, {W. K.} and Bernanke, {J. A.} and L. Borsu and Levine, {D. A.} and M. Ladanyi and C. Sander and D. Haussler and Benz, {C. C.} and Stuart, {J. M.} and Benz, {S. C.} and Sanborn, {J. Z.} and Vaske, {C. J.} and J. Zhu and C. Szeto and Scott, {G. K.} and C. Yau and Hoadley, {K. A.} and Y. Du and S. Balu and Hayes, {D. N.} and Perou, {C. M.} and Wilkerson, {M. D.} and N. Zhang and R. Akbani and Baggerly, {K. A.} and Yung, {W. K.} and Mills, {G. B.} and Weinstein, {J. N.} and R. Penny and T. Shelton and D. Grimm and M. Hatfield and S. Morris and P. Yena and P. Rhodes and M. Sherman and J. Paulauskis and S. Millis and A. Kahn and Greene, {J. M.} and R. Sfeir and Jensen, {M. A.} and J. Chen and J. Whitmore and S. Alonso and J. Jordan and A. Chu and Jinghui Zhang and A. Barker and C. Compton and G. Eley and M. Ferguson and P. Fielding and Gerhard, {D. S.} and R. Myles and C. Schaefer and {Mills Shaw}, {K. R.} and J. Vaught and Vockley, {J. B.} and Good, {P. J.} and Guyer, {M. S.} and B. Ozenberger and J. Peterson and E. Thomson",
year = "2011",
month = "6",
day = "30",
doi = "10.1038/nature10166",
language = "English (US)",
volume = "474",
pages = "609--615",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7353",

}

TY - JOUR

T1 - Integrated genomic analyses of ovarian carcinoma

AU - Bell, D.

AU - Berchuck, A.

AU - Birrer, M.

AU - Chien, J.

AU - Cramer, D. W.

AU - Dao, F.

AU - Dhir, R.

AU - Disaia, P.

AU - Gabra, H.

AU - Glenn, P.

AU - Godwin, A. K.

AU - Gross, J.

AU - Hartmann, L.

AU - Huang, M.

AU - Huntsman, D. G.

AU - Iacocca, M.

AU - Imielinski, M.

AU - Kalloger, S.

AU - Karlan, B. Y.

AU - Levine, D. A.

AU - Mills, Gordon

AU - Morrison, C.

AU - Mutch, D.

AU - Olvera, N.

AU - Orsulic, S.

AU - Park, K.

AU - Petrelli, N.

AU - Rabeno, B.

AU - Rader, J. S.

AU - Sikic, B. I.

AU - Smith-Mccune, K.

AU - Sood, A. K.

AU - Bowtell, D.

AU - Penny, R.

AU - Testa, J. R.

AU - Chang, K.

AU - Dinh, H. H.

AU - Drummond, J. A.

AU - Fowler, G.

AU - Gunaratne, P.

AU - Hawes, A. C.

AU - Kovar, C. L.

AU - Lewis, L. R.

AU - Morgan, M. B.

AU - Newsham, I. F.

AU - Santibanez, J.

AU - Reid, J. G.

AU - Trevino, L. R.

AU - Wu, Y. Q.

AU - Wang, M.

AU - Muzny, D. M.

AU - Wheeler, D. A.

AU - Gibbs, R. A.

AU - Getz, G.

AU - Lawrence, M. S.

AU - Cibulskis, K.

AU - Sivachenko, A. Y.

AU - Sougnez, C.

AU - Voet, D.

AU - Wilkinson, J.

AU - Bloom, T.

AU - Ardlie, K.

AU - Fennell, T.

AU - Baldwin, J.

AU - Gabriel, S.

AU - Lander, E. S.

AU - Ding, L.

AU - Fulton, R. S.

AU - Koboldt, D. C.

AU - McLellan, M. D.

AU - Wylie, T.

AU - Walker, J.

AU - O'Laughlin, M.

AU - Dooling, D. J.

AU - Fulton, L.

AU - Abbott, R.

AU - Dees, N. D.

AU - Zhang, Q.

AU - Kandoth, C.

AU - Wendl, M.

AU - Schierding, W.

AU - Shen, D.

AU - Harris, C. C.

AU - Schmidt, H.

AU - Kalicki, J.

AU - Delehaunty, K. D.

AU - Fronick, C. C.

AU - Demeter, R.

AU - Cook, L.

AU - Wallis, J. W.

AU - Lin, L.

AU - Magrini, V. J.

AU - Hodges, J. S.

AU - Eldred, J. M.

AU - Smith, S. M.

AU - Pohl, C. S.

AU - Vandin, F.

AU - Raphael, B. J.

AU - Weinstock, G. M.

AU - Mardis, E. R.

AU - Wilson, R. K.

AU - Meyerson, M.

AU - Winckler, W.

AU - Getz, G.

AU - Verhaak, R. G W

AU - Carter, S. L.

AU - Mermel, C. H.

AU - Saksena, G.

AU - Nguyen, H.

AU - Onofrio, R. C.

AU - Lawrence, M. S.

AU - Hubbard, D.

AU - Gupta, S.

AU - Crenshaw, A.

AU - Ramos, A. H.

AU - Ardlie, K.

AU - Chin, L.

AU - Protopopov, A.

AU - Zhang, Juinhua

AU - Kim, T. M.

AU - Perna, I.

AU - Xiao, Y.

AU - Zhang, H.

AU - Ren, G.

AU - Sathiamoorthy, N.

AU - Park, R. W.

AU - Lee, E.

AU - Park, P. J.

AU - Kucherlapati, R.

AU - Absher, D. M.

AU - Waite, L.

AU - Sherlock, G.

AU - Brooks, J. D.

AU - Li, J. Z.

AU - Xu, J.

AU - Myers, R. M.

AU - Laird, P. W.

AU - Cope, L.

AU - Herman, J. G.

AU - Shen, H.

AU - Weisenberger, D. J.

AU - Noushmehr, H.

AU - Pan, F.

AU - Triche, T.

AU - Berman, B. P.

AU - Spellman, Paul

AU - Buckley, J.

AU - Baylin, S. B.

AU - Spellman, P. T.

AU - Purdom, E.

AU - Neuvial, P.

AU - Bengtsson, H.

AU - Jakkula, L. R.

AU - Durinck, S.

AU - Han, J.

AU - Dorton, S.

AU - Marr, H.

AU - Choi, Y. G.

AU - Wang, V.

AU - Wang, N. J.

AU - Feiler, Heidi

AU - Conboy, J. G.

AU - Gray, Joe

AU - Feiler, H. S.

AU - Speed, T. P.

AU - Gray, J. W.

AU - Levine, D. A.

AU - Socci, N. D.

AU - Liang, Y.

AU - Taylor, B. S.

AU - Schultz, N.

AU - Borsu, L.

AU - Lash, A. E.

AU - Brennan, C.

AU - Viale, A.

AU - Sander, C.

AU - Ladanyi, M.

AU - Hoadley, K. A.

AU - Meng, S.

AU - Du, Y.

AU - Shi, Y.

AU - Li, L.

AU - Turman, Y. J.

AU - Zang, D.

AU - Helms, E. B.

AU - Balu, S.

AU - Zhou, X.

AU - Wu, J.

AU - Topal, M. D.

AU - Hayes, D. N.

AU - Perou, C. M.

AU - Getz, G.

AU - Voet, D.

AU - Saksena, G.

AU - Zhang, Junihua

AU - Zhang, H.

AU - Korkola, James

AU - Heiser, Laura

AU - Cibulskis, K.

AU - Hu, Zhi

AU - Sivachenko, A.

AU - Jing, R.

AU - Park, R. W.

AU - Liu, Y.

AU - Park, P. J.

AU - Noble, M.

AU - Chin, L.

AU - Carter, H.

AU - Kim, D.

AU - Karchin, R.

AU - Spellman, P. T.

AU - Purdom, E.

AU - Neuvial, P.

AU - Bengtsson, H.

AU - Durinck, S.

AU - Han, J.

AU - Korkola, J. E.

AU - Heiser, L. M.

AU - Cho, R. J.

AU - Hu, Z.

AU - Parvin, B.

AU - Speed, T. P.

AU - Gray, J. W.

AU - Schultz, N.

AU - Cerami, E.

AU - Taylor, B. S.

AU - Olshen, A.

AU - Reva, B.

AU - Antipin, Y.

AU - Shen, R.

AU - Mankoo, P.

AU - Sheridan, R.

AU - Ciriello, G.

AU - Chang, W. K.

AU - Bernanke, J. A.

AU - Borsu, L.

AU - Levine, D. A.

AU - Ladanyi, M.

AU - Sander, C.

AU - Haussler, D.

AU - Benz, C. C.

AU - Stuart, J. M.

AU - Benz, S. C.

AU - Sanborn, J. Z.

AU - Vaske, C. J.

AU - Zhu, J.

AU - Szeto, C.

AU - Scott, G. K.

AU - Yau, C.

AU - Hoadley, K. A.

AU - Du, Y.

AU - Balu, S.

AU - Hayes, D. N.

AU - Perou, C. M.

AU - Wilkerson, M. D.

AU - Zhang, N.

AU - Akbani, R.

AU - Baggerly, K. A.

AU - Yung, W. K.

AU - Mills, G. B.

AU - Weinstein, J. N.

AU - Penny, R.

AU - Shelton, T.

AU - Grimm, D.

AU - Hatfield, M.

AU - Morris, S.

AU - Yena, P.

AU - Rhodes, P.

AU - Sherman, M.

AU - Paulauskis, J.

AU - Millis, S.

AU - Kahn, A.

AU - Greene, J. M.

AU - Sfeir, R.

AU - Jensen, M. A.

AU - Chen, J.

AU - Whitmore, J.

AU - Alonso, S.

AU - Jordan, J.

AU - Chu, A.

AU - Zhang, Jinghui

AU - Barker, A.

AU - Compton, C.

AU - Eley, G.

AU - Ferguson, M.

AU - Fielding, P.

AU - Gerhard, D. S.

AU - Myles, R.

AU - Schaefer, C.

AU - Mills Shaw, K. R.

AU - Vaught, J.

AU - Vockley, J. B.

AU - Good, P. J.

AU - Guyer, M. S.

AU - Ozenberger, B.

AU - Peterson, J.

AU - Thomson, E.

PY - 2011/6/30

Y1 - 2011/6/30

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79959838081&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79959838081&partnerID=8YFLogxK

U2 - 10.1038/nature10166

DO - 10.1038/nature10166

M3 - Article

C2 - 21720365

AN - SCOPUS:79959838081

VL - 474

SP - 609

EP - 615

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7353

ER -