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

Academic Article

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.

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    Published In

    Keywords

  • Adult, Aged, Aged, 80 and over, Cell Cycle Checkpoints, Chromosomal Instability, Cohort Studies, Cystadenocarcinoma, Serous, DNA Damage, DNA Replication, Fallopian Tube Neoplasms, Female, Gene Expression Regulation, Neoplastic, Humans, Middle Aged, Mitosis, Ovarian Neoplasms, Phosphotransferases, Proteogenomics, Transcriptome, Tumor Suppressor Protein p53

    • Digital Object Identifier (doi)

    Pubmed Id

  • 27827322

    • Author List

  • McDermott JE; Arshad OA; Petyuk VA; Fu Y; Gritsenko MA; Clauss TR; Moore RJ; Schepmoes AA; Zhao R; Monroe ME

    • Volume

  • 1

    • Issue

  • 1