Integrated genomic analyses of ovarian carcinoma.

Integrated genomic analyses of ovarian carcinoma.
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DOI:
10.1038/nature10166
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发表时间:
2011-06-29
期刊:
影响因子:
64.8
通讯作者:
Thomson, E.
Thomson, E.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
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, G. B.;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, 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., Jr.;Berman, B. P.;Van den Berg, D. J.;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.;Ngai, J.;Conboy, J. G.;Parvin, B.;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.;Wu, C. J.;Shukla, S.;Cibulskis, K.;Lawrence, M. S.;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.;Shaw, K. R. Mills;Vaught, J.;Vockley, J. B.;Good, P. J.;Guyer, M. S.;Ozenberger, B.;Peterson, J.;Thomson, E.

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癌症基因组图集(TCGA)项目已分析了489个高级浆液卵巢腺癌(HGS-OVCA)中的mRNA表达,miRNA表达,启动子甲基化和DNA拷贝数,以及这些肿瘤中316个基因的外显子的DNA序列的mRNA表达,促进剂,促进甲基化和DNA拷贝数。 。这些结果表明,HGS-OVCA的特征是几乎所有肿瘤中的TP53突变(96%)。低患病率,但在包括NF1,BRCA1,BRCA2,RB1和CDK12在内的9个其他基因中进行了统计复发的体细胞突变; 113焦点DNA拷贝数畸变;以及涉及168个基因的启动子甲基化事件。分析描述了四个卵巢癌转录亚型,三个miRNA亚型,四个启动子甲基化亚型,一种与生存持续时间相关的转录特征,并为对BRCA1/2和CCNE1差异的肿瘤的影响提供了新的启示。途径分析表明,同源重组在大约一半的肿瘤中有缺陷,并且Notch和FoxM1信号与浆液性卵巢癌病理生理学有关。
The Cancer Genome Atlas (TCGA) project has analyzed mRNA expression, miRNA expression, promoter methylation, and DNA copy number in 489 high-grade serous ovarian adenocarcinomas (HGS-OvCa) and the DNA sequences of exons from coding genes in 316 of these tumors. These results show that HGS-OvCa is characterized by TP53 mutations in almost all tumors (96%); low prevalence but statistically recurrent somatic mutations in 9 additional 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 miRNA subtypes, four promoter methylation subtypes, a transcriptional signature associated with survival duration and shed new light on the impact on survival of tumors with BRCA1/2 and CCNE1 aberrations. Pathway analyses suggested that homologous recombination is defective in about half of tumors, and that Notch and FOXM1 signaling are involved in serous ovarian cancer pathophysiology.
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