Integrated genomic analyses of ovarian carcinoma. [Nature. 2011] - PubMed result

Integrated genomic analyses of ovarian carcinoma. [Nature. 2011] - PubMed result: "Nature. 2011 Jun 29;474(7353):609-15. doi: 10.1038/nature10166.
Integrated genomic analyses of ovarian carcinoma.
Cancer Genome Atlas Research Network.
Collaborators (297)

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 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, 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 LL, 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 RG, 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 M, Waite L, Sherlock G, Brooks JD, Li JZ, Xu J, Myers RM, Laird W, Cope L, Herman JG, Shen H, Weisenberger DJ, Noushmehr H, Pan F, Triche T Jr, Berman BP, Van Den Berg DJ, 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, Ngai J, Conboy JG, Parvin B, Feiler HS, Speed TP, Gray JW, Levine A, 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, Wu CJ, Shukla S, Cibulskis K, Lawrence MS, 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.

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.

PMID:
21720365
[PubMed - in process]

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