Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer

To provide a detailed analysis of the molecular com-ponents and underlying mechanisms associatedwith ovarian cancer, we performed a comprehensivemass-spectrometry-based proteomic characteriza-tion of 174 ovarian tumors previously analyzed byThe Cancer Genome Atlas (TCGA), of which 169were high-grade serous carcinomas (HGSCs). Inte-grating our proteomic measurements with thegenomic data yielded a number of insights into dis-ease, such as how different copy-number alterna-tionsinfluencetheproteome,theproteinsassociatedwith chromosomal instability, the sets of signalingpathways that diverse genome rearrangementsconverge on, and the ones most associated withshort overall survival. Specific protein acetylationsassociated with homologous recombination defi-ciency suggest a potential means for stratifying pa-tients for therapy. In addition to providing a valuableresource,thesefindingsprovideaviewofhowtheso-maticgenomedrivesthecancerproteomeandasso-ciations between protein and post-translationalmodification levels and clinical outcomes in HGSC.