Integrated Proteogenomic Characterization of Clear Cell Renal Cell Carcinoma

Published in Cell, 2019

Recommended citation: Clark DJ, Dhanasekaran SM, Petralia F, et al. Integrated Proteogenomic Characterization of Clear Cell Renal Cell Carcinoma [published correction appears in Cell. 2020 Jan 9;180(1):207]. Cell. 2019;179(4):964-983.e31. doi:10.1016/j.cell.2019.10.007

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To elucidate the deregulated functional modules that drive clear cell renal cell carcinoma (ccRCC), we performed comprehensive genomic, epigenomic, transcriptomic, proteomic, and phosphoproteomic characterization of treatment-naive ccRCC and paired normal adjacent tissue samples. Genomic analyses identified a distinct molecular subgroup associated with genomic instability. Integration of proteogenomic measurements uniquely identified protein dysregulation of cellular mechanisms impacted by genomic alterations, including oxidative phosphorylation-related metabolism, protein translation processes, and phospho-signaling modules. To assess the degree of immune infiltration in individual tumors, we identified microenvironment cell signatures that delineated four immune-based ccRCC subtypes characterized by distinct cellular pathways. This study reports a large-scale proteogenomic analysis of ccRCC to discern the functional impact of genomic alterations and provides evidence for rational treatment selection stemming from ccRCC pathobiology.