Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer

被引：691

作者：

Zhang, Hui ^{[1
]}

Liu, Tao ^{[2
]}

Zhang, Zhen ^{[1
]}

Payne, Samuel H. ^{[2
]}

Zhang, Bai ^{[1
]}

McDermott, Jason E. ^{[2
]}

Zhou, Jian-Ying ^{[1
]}

Petyuk, Vladislav A. ^{[2
]}

Chen, Li ^{[1
]}

Ray, Debjit ^{[2
]}

Sun, Shisheng ^{[1
]}

Yang, Feng ^{[2
]}

Chen, Lijun ^{[1
]}

Wang, Jing ^{[3
]}

Shah, Punit ^{[1
]}

Cha, Seong Won ^{[4
]}

Aiyetan, Paul ^{[1
]}

Woo, Sunghee ^{[4
]}

Tian, Yuan ^{[1
]}

Gritsenko, Marina A. ^{[2
]}

Clauss, Therese R. ^{[2
]}

Choi, Caitlin ^{[1
]}

Monroe, Matthew E. ^{[2
]}

Thomas, Stefani ^{[1
]}

Nie, Song ^{[2
]}

Wu, Chaochao ^{[2
]}

Moore, Ronald J. ^{[2
]}

Yu, Kun-Hsing ^{[5
,6
]}

Tabb, David L. ^{[3
]}

Fenyo, David ^{[7
,8
]}

Bafna, Vineet ^{[9
]}

Wang, Yue ^{[10
]}

Rodriguez, Henry ^{[11
]}

Boja, Emily S. ^{[11
]}

Hiltke, Tara ^{[11
]}

Rivers, Robert C. ^{[11
]}

Sokoll, Lori ^{[1
]}

Zhu, Heng ^{[1
]}

Shih, Ie-Ming ^{[12
]}

Cope, Leslie ^{[13
]}

Pandey, Akhilesh ^{[14
]}

Zhang, Bing ^{[3
]}

Snyder, Michael P. ^{[6
]}

Levine, Douglas A. ^{[15
]}

Smith, Richard D. ^{[2
]}

Chan, Daniel W. ^{[1
]}

Rodland, Karin D. ^{[2
]}

机构：

[1] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21231 USA

[2] Pacific Northwest Natl Lab, Div Biol Sci, Richland, WA 99352 USA

[3] Vanderbilt Univ, Dept Biomed Informat, Sch Med, Nashville, TN 37203 USA

[4] Univ Calif San Diego, Dept Elect & Comp Engn, San Diego, CA 92093 USA

[5] Stanford Univ, Biomed Informat Training Program, Sch Med, Stanford, CA 94305 USA

[6] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA

[7] NYU, Sch Med, Ctr Hlth Informat & Bioinformat, New York, NY 10016 USA

[8] NYU, Sch Med, Dept Biochem & Mol Pharmacol, New York, NY 10016 USA

[9] Univ Calif San Diego, Dept Comp Sci & Engn, San Diego, CA 92093 USA

[10] Virginia Polytech Inst & State Univ, Bradley Dept Elect & Comp Engn, Arlington, VA 22203 USA

[11] NCI, Off Canc Clin Prote Res, Bethesda, MD 20892 USA

[12] Johns Hopkins Med Inst, Dept Gynecol & Obstet, Baltimore, MD 21231 USA

[13] Johns Hopkins Med Inst, Dept Oncol, Baltimore, MD 21231 USA

[14] Johns Hopkins Med Inst, McKusick Nathans Inst Genet Med, Baltimore, MD 21287 USA

[15] NYU, Laura & Isaac Perlmutter Canc Ctr, Dept Gynecol Oncol, Langone Med Ctr, New York, NY 10016 USA

来源：

CELL | 2016年 / 166卷 / 03期

关键词：

EPITHELIAL OVARIAN; PHASE-II; HISTONE DEACETYLASE; PROTEIN EXPRESSION; CARCINOMA; REPAIR; BELINOSTAT; STRATEGIES; MUTATIONS; ABUNDANCE;

D O I：

10.1016/j.cell.2016.05.069

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

To provide a detailed analysis of the molecular components and underlying mechanisms associated with ovarian cancer, we performed a comprehensive mass-spectrometry-based proteomic characterization of 174 ovarian tumors previously analyzed by The Cancer Genome Atlas (TCGA), of which 169 were high-grade serous carcinomas (HGSCs). Integrating our proteomic measurements with the genomic data yielded a number of insights into disease, such as how different copy-number alternations influence the proteome, the proteins associated with chromosomal instability, the sets of signaling pathways that diverse genome rearrangements converge on, and the ones most associated with short overall survival. Specific protein acetylations associated with homologous recombination deficiency suggest a potential means for stratifying patients for therapy. In addition to providing a valuable resource, these findings provide a view of how the somatic genome drives the cancer proteome and associations between protein and post-translational modification levels and clinical outcomes in HGSC.

引用

页码：755 / 765

页数：11

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