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.
Bibliographical noteFunding Information:
This work was supported by National Cancer Institute (NCI) CPTAC awards U24CA160019 and U24CA160036 and by NIH grant P41GM103493 . The PNNL proteomics work described herein was performed in the Environmental Molecular Sciences Laboratory, a U.S. Department of Energy (DOE) National Scientific User Facility located at PNNL in Richland, WA. PNNL is a multi-program national laboratory operated by the Battelle Memorial Institute for the DOE under contract DE-AC05-76RL01830 . Genomics data for this study were generated by the TCGA Pilot Project, established by the NCI and the National Human Genome Research Institute.
© 2016 Elsevier Inc.