Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer
Open accessAbstract
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. VIDEO ABSTRACT.
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CPTAC applied standards and workflows to tumours previously genomically characterized by The Cancer Genome Atlas, pioneered the integration of proteomics with genomics to produce a more unified and comprehensive understanding of cancer biology, and implemented its transition into cancer clinical research studies.
“CPTAC applied these standards and workflows to tumours previously genomically characterized by The Cancer Genome Atlas. In doing so, CPTAC pioneered the integration of proteomics with genomics (i.e., proteogenomics) to produce a more unified and comprehensive understanding of cancer biology and implemented its transition into cancer clinical research studies96,104,105.”
From A high-stringency blueprint of the human proteome (2020) · cites this paper as [105]
The flagship efforts of the Cancer Proteomics Consortium, CPTAC, have brought targeted proteomics and proteogenomics into regular use and produced major studies on ovarian, breast, and colorectal cancer.
“The flagship efforts of the Cancer Proteomics Consortium, CPTAC, have brought targeted proteomics and proteogenomics into regular use and produced major studies on ovarian ( 10 ), breast ( 11 ), and colorectal cancer ( 12 ).”
From The Human Proteoform Project: Defining the human proteome (2021) · cites this paper as [10]
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- Authors
- Zhang, H., Liu, T., Zhang, Z., Payne, S. H., Zhang, B., McDermott, J. E., Zhou, J.-Y., Petyuk, V. A., Chen, L., Ray, D., Sun, S., Yang, F., Chen, L., Wang, J., Shah, P., Cha, S. W., Aiyetan, P., Woo, S., Tian, Y., Gritsenko, M. A., Clauss, T. R., Choi, C., Monroe, M. E., Thomas, S., Nie, S., Wu, C., Moore, R. J., Yu, K.-H., Tabb, D. L., Fenyö, D., Bafna, V., Wang, Y., Rodriguez, H., Boja, E. S., Hiltke, T., Rivers, R. C., Sokoll, L., Zhu, H., Shih, I.-M., Cope, L., Pandey, A., Zhang, B., Snyder, M. P., Levine, D. A., Smith, R. D., Chan, D. W., Rodland, K. D., Carr, S. A., Gillette, M. A., Klauser, K. R., Kuhn, E., Mani, D. R., Mertins, P., Ketchum, K. A., Thangudu, R., Cai, S., Oberti, M., Paulovich, A. G., Whiteaker, J. R., Edwards, N. J., McGarvey, P. B., Madhavan, S., Wang, P., Chan, D. W., Pandey, A., Shih, I.-M., Zhang, H., Zhang, Z., Zhu, H., Cope, L., Whiteley, G. A., Skates, S. J., White, F. M., Levine, D. A., Boja, E. S., Kinsinger, C. R., Hiltke, T., Mesri, M., Rivers, R. C., Rodriguez, H., Shaw, K. M., Stein, S. E., Fenyo, D., Liu, T., McDermott, J. E., Payne, S. H., Rodland, K. D., Smith, R. D., Rudnick, P., Snyder, M., Zhao, Y., Chen, X., Ransohoff, D. F., Hoofnagle, A. N., Liebler, D. C., Sanders, M. E., Shi, Z., Slebos, R. J. C., Tabb, D. L., Zhang, B., Zimmerman, L. J., Wang, Y., Davies, S. R., Ding, L., Ellis, M. J. C., & Townsend, R. R.
- Affiliations
- Vanderbilt University (US)
- Pacific Northwest National Laboratory (US)
- Johns Hopkins Medicine (US)
- University of California San Diego (US)
- Stanford Medicine (US)
- National Cancer Institute (US)
- Virginia Tech (US)
- NYU Langone Health (US)
- Johns Hopkins University (US)
- ORCID
- Zhang, Bai
- Petyuk, Vladislav A.
- Chen, Li
- Ray, Debjit
- Sun, Shisheng
- Yang, Feng
- Chen, Lijun
- Wang, Jing
- Cha, Seong Won
- Aiyetan, Paul
- Tian, Yuan
- Gritsenko, Marina A.
- Monroe, Matthew E.
- Thomas, Stefani
- Nie, Song
- Moore, Ronald J.
- Yu, Kun-Hsing
- Bafna, Vineet
- Sokoll, Lori
- Carr, Steven A.
- Gillette, Michael A.
- Kuhn, Eric
- Mani, D.R.
- Mertins, Philipp
- Ketchum, Karen A.
- Thangudu, Ratna
- Cai, Shuang
- Oberti, Mauricio
- Paulovich, Amanda G.
- Whiteaker, Jeffrey R.
- Edwards, Nathan J.
- McGarvey, Peter B.
- Madhavan, Subha
- Wang, Pei
- Skates, Steven J.
- White, Forest M.
- Kinsinger, Christopher R.
- Mesri, Mehdi
- Stein, Stephen E.
- Rudnick, Paul
- Zhao, Yingming
- Chen, Xian
- Ransohoff, David F.
- Hoofnagle, Andrew N.
- Liebler, Daniel C.
- Sanders, Melinda E.
- Shi, Zhiao
- Slebos, Robbert J.C.
- Zimmerman, Lisa J.
- Davies, Sherri R.
- Ding, Li
- Ellis, Matthew J.C.
- Townsend, R. Reid
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-07
- Volume
- 166
- Issue
- 3
- Pages
- 755-765
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4967013
- OpenAlex
- W2464880876
- Cited by
- 1,029
- References
- 47
- Citations by year
- 2026: 72 · 2025: 103 · 2024: 100 · 2023: 106 · 2022: 90 · 2021: 139 · 2020: 111 · 2019: 107 · 2018: 101 · 2017: 85 · 2016: 14
- FWCI
- 135.47
- Type
- journal article
- Language
- en
- Update notices
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- Funders
- National Institutes of Health (P41GM103493)
- U.S. Department of Energy (DE-AC05-76RL01830)
- Battelle
- National Cancer Institute (U24CA160019, U24CA160036)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Keywords
- high-grade serous ovarian cancer, proteogenomics, tumor proteome, copy number alterations, chromosomal instability, genome rearrangement, signaling pathways, overall survival, protein acetylation, homologous recombination deficiency, post-translational modification, patient stratification
- MeSH terms
- Acetylation, DNA Repair, DNA, Neoplasm, Female, Humans, Neoplasm Proteins, Ovarian Neoplasms, Phosphoproteins, Protein Processing, Post-Translational, Mass Spectrometry, Survival Analysis, Neoplasms, Cystic, Mucinous, and Serous, Gene Dosage, Proteome, Chromosomal Instability
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