Cell
Volume 166, Issue 3, 28 July 2016, Pages 755-765
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Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer

https://doi.org/10.1016/j.cell.2016.05.069Get rights and content
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Highlights

  • Comprehensive proteomic characterization of 174 ovarian tumors are analyzed

  • Copy-number alterations affect the proteome in trans, converging on pathways

  • Acetylation of histone H4 correlates with homologous repair deficiency status

  • Protein and phosphoprotein abundance identifies pathways associated with survival

Summary

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.

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