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Cell. 2016 Jul 28;166(3):755-765. doi: 10.1016/j.cell.2016.05.069. Epub 2016 Jun 29.

Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer.

Author information

1
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
2
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
3
Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN 37203, USA.
4
Department of Electrical and Computer Engineering, University of California, San Diego, La Jolla, CA 92093, USA.
5
Biomedical Informatics Training Program, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
6
Center for Health Informatics and Bioinformatics and Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA.
7
Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA 92093, USA.
8
Bradley Department of Electrical and Computer Engineering, Virginia Polytechnic Institute and State University, Arlington, VA 22203, USA.
9
Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD 20892, USA.
10
Department of Gynecology and Obstetrics, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
11
Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
12
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
13
Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
14
Department of Gynecologic Oncology, Laura and Isaac Perlmutter Cancer Centre, NYU Langone Medical Center, New York, NY 10016, USA.
15
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA. Electronic address: dchan@jhmi.edu.
16
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA. Electronic address: karin.rodland@pnnl.gov.

Abstract

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.

PMID:
27372738
PMCID:
PMC4967013
DOI:
10.1016/j.cell.2016.05.069
[Indexed for MEDLINE]
Free PMC Article

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