Cell
Volume 179, Issue 4, 31 October 2019, Pages 964-983.e31
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Integrated Proteogenomic Characterization of Clear Cell Renal Cell Carcinoma

https://doi.org/10.1016/j.cell.2019.10.007Get rights and content
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Highlights

  • Integrated proteogenomic characterization in 103 ccRCC cases

  • Delineation of chromosomal translocation events leading to chromosome 3p loss

  • Tumor-specific proteomic/phosphoproteomic alterations unrevealed by mRNA analysis

  • Immune-based subtypes of ccRCC defined by mRNA, proteome, and phosphoproteome

Summary

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.

Keywords

ccRCC
renal carcinoma
proteogenomics
proteomics
immune infiltration
tumor microenvironment
phosphoproteomics
drug targets
chromosomal translocation
CPTAC

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These authors contributed equally

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These authors contributed equally

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