Integrated genomic analyses of ovarian carcinoma. Academic Article

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Overview

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.

authors

• Cancer Genome Atlas Research Network

collaborators

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

publication date

• June 2011

published in

• Nature  Journal
• Nature  Journal

Research

keywords

• Aged
• Carcinoma
• DNA Methylation
• Female
• Gene Dosage
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Genomics
• Humans
• MicroRNAs
• Middle Aged
• Mutation
• Ovarian Neoplasms
• RNA, Messenger

Identity

Digital Object Identifier (DOI)

• https://doi.org/10.1038/nature10166

PubMed ID

• 21720365

Additional Document Info

start page

• 609

end page

• 615

volume

• 474

number

• 7353