@article{8357e4d599d44ce58f1d382d4d2cfb07,
title = "Proteogenomic Characterization of Ovarian HGSC Implicates Mitotic Kinases, Replication Stress in Observed Chromosomal Instability",
abstract = "In the absence of a dominant driving mutation other than uniformly present TP53 mutations, deeper understanding of the biology driving ovarian high-grade serous cancer (HGSC) requires analysis at a functional level, including post-translational modifications. Comprehensive proteogenomic and phosphoproteomic characterization of 83 prospectively collected ovarian HGSC and appropriate normal precursor tissue samples (fallopian tube) under strict control of ischemia time reveals pathways that significantly differentiate between HGSC and relevant normal tissues in the context of homologous repair deficiency (HRD) status. In addition to confirming key features of HGSC from previous studies, including a potential survival-associated signature and histone acetylation as a marker of HRD, deep phosphoproteomics provides insights regarding the potential role of proliferation-induced replication stress in promoting the characteristic chromosomal instability of HGSC and suggests potential therapeutic targets for use in precision medicine trials.",
keywords = "fallopian tube, homologous repair deficiency, ovarian cancer, phosphoproteomics, proteogenomics, proteomics, replication stress",
author = "{Clinical Proteomic Tumor Analysis Consortium} and McDermott, {Jason E.} and Arshad, {Osama A.} and Petyuk, {Vladislav A.} and Yi Fu and Gritsenko, {Marina A.} and Clauss, {Therese R.} and Moore, {Ronald J.} and Schepmoes, {Athena A.} and Rui Zhao and Monroe, {Matthew E.} and Michael Schnaubelt and Tsai, {Chia Feng} and Payne, {Samuel H.} and Chen Huang and Wang, {Liang Bo} and Steven Foltz and Matthew Wyczalkowski and Yige Wu and Ehwang Song and Brewer, {Molly A.} and Mathangi Thiagarajan and Kinsinger, {Christopher R.} and Robles, {Ana I.} and Boja, {Emily S.} and Henry Rodriguez and Chan, {Daniel W.} and Bing Zhang and Zhen Zhang and Li Ding and Smith, {Richard D.} and Tao Liu and Rodland, {Karin D.}",
note = "Funding Information: This work was supported by grants U24CA160019, U24CA160036, and U24CA210955 from the National Institute of General Medical Sciences (NCI) CPTAC , and P41GM103493 from the National Institutes of Health . The proteomics work described herein was performed in the Environmental Molecular Sciences Laboratory (grid.436923.9), a US Department of Energy (DOE) national scientific user facility located at the Pacific Northwest National Laboratory (PNNL) in Richland, Washington. PNNL is a multi-program national laboratory operated by Battelle Memorial Institute for the DOE under Contract DE-AC05-76RL01830. Publisher Copyright: {\textcopyright} 2020 The Author(s)",
year = "2020",
month = apr,
day = "21",
doi = "10.1016/j.xcrm.2020.100004",
language = "English",
volume = "1",
journal = "Cell Reports Medicine",
issn = "2666-3791",
number = "1",
}