title: Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer.
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.
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Payne
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors.forename: Bai
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
authors.forename: Jason E
authors.initials: JE
authors.lastname: McDermott
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors.forename: Jian-Ying
authors.initials: JY
authors.lastname: Zhou
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
authors.forename: Vladislav A
authors.initials: VA
authors.lastname: Petyuk
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
authors.forename: Debjit
authors.initials: D
authors.lastname: Ray
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors.forename: Shisheng
authors.initials: S
authors.lastname: Sun
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors.forename: Lijun
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN 37203, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors.forename: Punit
authors.initials: P
authors.lastname: Shah
authors.affiliation: Department of Electrical and Computer Engineering, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Seong Won
authors.initials: SW
authors.lastname: Cha
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Aiyetan
authors.affiliation: Department of Electrical and Computer Engineering, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Sunghee
authors.initials: S
authors.lastname: Woo
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
authors.forename: Marina A
authors.initials: MA
authors.lastname: Gritsenko
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
authors.forename: Therese R
authors.initials: TR
authors.lastname: Clauss
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors.forename: Caitlin
authors.initials: C
authors.lastname: Choi
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Monroe
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors.forename: Stefani
authors.initials: S
authors.lastname: Thomas
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
authors.forename: Song
authors.initials: S
authors.lastname: Nie
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
authors.forename: Chaochao
authors.initials: C
authors.lastname: Wu
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Moore
authors.affiliation: 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.
authors.forename: Kun-Hsing
authors.initials: KH
authors.lastname: Yu
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN 37203, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Tabb
authors.affiliation: Center for Health Informatics and Bioinformatics and Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: David
authors.initials: D
authors.lastname: Fenyö
authors.affiliation: Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Vineet
authors.initials: V
authors.lastname: Bafna
authors.affiliation: Bradley Department of Electrical and Computer Engineering, Virginia Polytechnic Institute and State University, Arlington, VA 22203, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Henry
authors.initials: H
authors.lastname: Rodriguez
authors.affiliation: Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Emily S
authors.initials: ES
authors.lastname: Boja
authors.affiliation: Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Tara
authors.initials: T
authors.lastname: Hiltke
authors.affiliation: Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Rivers
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors.forename: Lori
authors.initials: L
authors.lastname: Sokoll
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Gynecology and Obstetrics, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors.forename: Ie-Ming
authors.initials: IM
authors.lastname: Shih
authors.affiliation: Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Cope
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
authors.forename: Akhilesh
authors.initials: A
authors.lastname: Pandey
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN 37203, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Snyder
authors.affiliation: Department of Gynecologic Oncology, Laura and Isaac Perlmutter Cancer Centre, NYU Langone Medical Center, New York, NY 10016, USA.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Levine
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Smith
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA. Electronic address: dchan@jhmi.edu.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Chan
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA. Electronic address: karin.rodland@pnnl.gov.
authors.forename: Karin D
authors.initials: KD
authors.lastname: Rodland
mesh_terms: D000107:Acetylation; D043171:Chromosomal Instability; D004260:DNA Repair; D004273:DNA, Neoplasm; D005260:Female; D018628:Gene Dosage; D006801:Humans; D013058:Mass Spectrometry; D009363:Neoplasm Proteins / Q000235:genetics*; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics; D011499:Protein Processing, Post-Translational; D020543:Proteome; D016019:Survival Analysis
chemical_list: D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D020543:Proteome