Integrated genomic analyses of ovarian carcinoma

Autor: Bell, D, Berchuck, A, Birrer, M, Chien, J, Cramer, DW, Dao, F, Dhir, R, DiSaia, P, Gabra, H, Glenn, P, Godwin, AK, Triche, T, Berman, BP, Van den Berg, DJ, Buckley, J, Baylin, SB, Zhang, J, Spellman, PT, Purdom, E, Iacocca, M, Shelton, T, Voet, D, Neuvial, P, Bengtsson, H, Jakkula, LR, Durinck, S, Han, J, Dorton, S, Marr, H, Zhang, H, Choi, YG, Wang, V, Wilkinson, J, Nguyen, H, Wang, NJ, Imielinski, M, Ngai, J, Conboy, JG, Parvin, B, Feiler, HS, Speed, TP, Gray, JW, Wu, CJ, Bloom, T, Levine, DA, Li, L, Socci, ND, Liang, Y, Taylor, BS, Kalloger, S, Schultz, N, Borsu, L, Lash, AE, Brennan, C, Ardlie, K, Viale, A, Shukla, S, Grimm, D, Sander, C, Ladanyi, M, Hoadley, KA, Meng, S, Du, Y, Karlan, BY, Shi, Y, Fennell, T, Cibulskis, K, Lawrence, MS, Meyerson, M, Hatfield, M, Mills, GB, Sivachenko, A, Jing, R, Park, RW, Liu, Y, Park, PJ, Ramos, AH, Noble, M, Chin, L, Carter, H, Kim, D, Morris, S, Winckler, W, Karchin, R, Morrison, C, Baldwin, J, Korkola, JE, Yena, P, Heiser, LM, Getz, G, Cho, RJ, Hu, Z, Gabriel, S, Mutch, D, Cerami, E, Rhodes, P, Olshen, A, Verhaak, RGW, Lander, ES, Reva, B, Antipin, Y, Shen, R, Olvera, N, Mankoo, P, Sheridan, R, Ciriello, G, Sherman, M, Chang, WK, Bernanke, JA, Hayes, DN, Carter, SL, Haussler, D, Orsulic, S, Benz, CC, Paulauskis, J, Stuart, JM, Zhang, N, Benz, SC, Sanborn, JZ, Vaske, CJ, Mermel, CH, Zhu, J, Szeto, C, Scott, GK, Yau, C, Rabeno, B, Ding, L, Park, K, Balu, S, Perou, CM, Saksena, G, Wilkerson, MD, Millis, S, Kahn, A, Turman, YJ, Fulton, RS, Onofrio, RC, Greene, JM, Sfeir, R, Jensen, MA, Chen, J, Whitmore, J, Alonso, S, Jordan, J, Chu, A, Rader, JS, Koboldt, DC, Zang, D, Gross, J, Barker, A, Compton, C, Eley, G, Ferguson, M, Fielding, P, Gerhard, DS, Myles, R, McLellan, MD, Schaefer, C, Helms, EB, Shaw, KRM, Sikic, BI, Vaught, J, Vockley, JB, Good, PJ, Guyer, MS, Ozenberger, B, Wylie, T, Peterson, J, Thomson, E, Smith-McCune, K, Sood, AK, Bowtell, D, Hubbard, D, Penny, R, Testa, JR, Chang, K, Walker, J, Dinh, HH, Drummond, JA, Fowler, G, Zhou, X, Gunaratne, P, Hawes, AC, Kovar, CL, Lewis, LR, Gupta, S, Morgan, MB, O'Laughlin, M, Newsham, IF, Santibanez, J, Reid, JG, Trevino, LR, Wu, J, Wu, Y-Q, Wang, M, Muzny, DM, Wheeler, DA, Gibbs, RA, Crenshaw, A, Sivachenko, AY, Topal, MD, Sougnez, C, Dooling, DJ, Fulton, L, Akbani, R, Abbott, R, Dees, ND, Zhang, Q, Kandoth, C, Wendl, M, Schierding, W, Shen, D, Harris, CC, Baggerly, KA, Schmidt, H, Wilson, RK, Kalicki, J, Delehaunty, KD, Fronick, CC, Demeter, R, Cook, L, Wallis, JW, Lin, L, Magrini, VJ, Yung, WK, Hodges, JS, Protopopov, A, Eldred, JM, Smith, SM, Pohl, CS, Vandin, F, Raphael, BJ, Weinstock, GM, Mardis, R, Kim, TM, Hartmann, L, Perna, I, Xiao, Y, Ren, G, Sathiamoorthy, N, Petrelli, N, Lee, E, Kucherlapati, R, Absher, DM, Huang, M, Waite, L, Sherlock, G, Brooks, JD, Li, JZ, Weinstein, JN, Xu, J, Myers, RM, Laird, PW, Cope, L, Herman, JG, Shen, H, Huntsman, DG, Weisenberger, DJ, Noushmehr, H, Pan, F
Přispěvatelé: Massachusetts Institute of Technology. Department of Biology, Lander, Eric S., Meyerson, Matthew L.
Jazyk: angličtina
Rok vydání: 2010
Předmět:
endocrine system diseases
Serous carcinoma
Messenger
Gene Dosage
Cancer Genome Atlas Research Network
GYNECOLOGIC-ONCOLOGY-GROUP
GRADE SEROUS CARCINOMA
0302 clinical medicine
Ovarian carcinoma
Aged
Carcinoma
DNA Methylation
Female
Gene Expression Profiling
Gene Expression Regulation
Neoplastic

Humans
MicroRNAs
Middle Aged
Mutation
Ovarian Neoplasms
RNA
Messenger

Genomics
Multidisciplinary
Genetics
HYBRID SELECTION
0303 health sciences
female genital diseases and pregnancy complications
3. Good health
Multidisciplinary Sciences
Serous fluid
BRCA MUTATION CARRIERS
030220 oncology & carcinogenesis
DNA methylation
PARP inhibitor
Science & Technology - Other Topics
General Science & Technology
Biology
Article
03 medical and health sciences
CLEAR-CELL CARCINOMA
MD Multidisciplinary
microRNA
HIGH-THROUGHPUT ANNOTATION
medicine
DRIVER MUTATIONS
Gene
030304 developmental biology
Neoplastic
Science & Technology
MUTANT-CELLS
SOMATIC MUTATIONS
medicine.disease
CANCER STATISTICS
Gene Expression Regulation
Cancer research
RNA
Ovarian cancer
Zdroj: PMC
Nature
Popis: 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.
National Institutes of Health (U.S.) (Grant U54HG003067)
National Institutes of Health (U.S.) (Grant U54HG003273)
National Institutes of Health (U.S.) (Grant U54HG003079)
National Institutes of Health (U.S.) (Grant U24CA126543)
National Institutes of Health (U.S.) (Grant U24CA126544)
National Institutes of Health (U.S.) (Grant U24CA126546)
National Institutes of Health (U.S.) (Grant U24CA126551)
National Institutes of Health (U.S.) (Grant U24CA126554)
National Institutes of Health (U.S.) (Grant U24CA126561)
National Institutes of Health (U.S.) (Grant U24CA126563)
National Institutes of Health (U.S.) (Grant U24CA143882)
National Institutes of Health (U.S.) (Grant U24CA143731)
National Institutes of Health (U.S.) (Grant U24CA143835)
National Institutes of Health (U.S.) (Grant U24CA143845)
National Institutes of Health (U.S.) (Grant U24CA143858)
National Institutes of Health (U.S.) (Grant U24CA144025)
National Institutes of Health (U.S.) (Grant U24CA143866)
National Institutes of Health (U.S.) (Grant U24CA143867)
National Institutes of Health (U.S.) (Grant U24CA143848)
National Institutes of Health (U.S.) (Grant U24CA143843)
National Institutes of Health (U.S.) (Grant R21CA135877)
Databáze: OpenAIRE