Proteogenomic Characterization of Ovarian HGSC Implicates Mitotic Kinases, Replication Stress in Observed Chromosomal Instability

Cell Reports Medicine

Osama A. Arshad¹  Tao Liu²  Matthew Wyczalkowski²  Vladislav A. Petyuk³  Matthew E. Monroe⁴  Ronald J. Moore⁴  Michael Schnaubelt⁴  Chia-Feng Tsai⁴  Jason E. McDermott⁴  Rui Zhao⁴  Yi Fu⁴  Chen Huang⁴  Marina A. Gritsenko⁴  Christopher R. Kinsinger⁴  Athena A. Schepmoes⁴  Liang-Bo Wang⁵  Ana I. Robles⁶  Karin D. Rodland⁷  Li Ding⁷  Samuel H. Payne⁷  Therese R. Clauss⁷  Emily S. Boja⁸  Richard D. Smith⁹  Steven Foltz⁹  Bing Zhang^1,10  Henry Rodriguez^1,10  Zhen Zhang^1,10  Daniel W. Chan^1,10  Mathangi Thiagarajan^1,11  Ehwang Song^1,11  Molly A. Brewer^1,11  Yige Wu^1,11 

[1] Department of Molecular Microbiology and Immunology, Oregon Health &Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA;Science University, Portland, OR 97201, USA;Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA;Department of Biology, Brigham Young University, Provo, UT 84602, USA;Department of Obstetrics and Gynecology, University of Connecticut, Farmington, CT 06030, USA;Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA;Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA;Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA;Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD 20892, USA;The McDonnell Genome Institute, Washington University in St. Louis, St Louis, MO 63108, USA;

关键词: proteogenomics;    ovarian cancer;    phosphoproteomics;    proteomics;    fallopian tube;    homologous repair deficiency;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: 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.

【 授权许可】

Unknown