The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

Authors

Christopher J. Ricketts, National Cancer Institute (NCI)
Aguirre A. De Cubas, Vanderbilt University School of Medicine
Huihui Fan, Van Andel Research Institute
Christof C. Smith, The University of North Carolina at Chapel Hill
Martin Lang, National Cancer Institute (NCI)
Ed Reznik, Memorial Sloan-Kettering Cancer Center
Reanne Bowlby, Canada‘s Michael Smith Genome Sciences Centre
Ewan A. Gibb, Canada‘s Michael Smith Genome Sciences Centre
Rehan Akbani, University of Texas MD Anderson Cancer Center
Rameen Beroukhim, Massachusetts Institute of Technology
Donald P. Bottaro, National Cancer Institute (NCI)
Toni K. Choueiri, Dana-Farber Cancer Institute
Richard A. Gibbs, Baylor College of Medicine
Andrew K. Godwin, University of Kansas Medical Center
Scott Haake, Vanderbilt University School of Medicine
A. Ari Hakimi, Memorial Sloan-Kettering Cancer Center
Elizabeth P. Henske, Brigham and Women's Hospital
James J. Hsieh, Washington University School of Medicine in St. Louis
Thai H. Ho, Mayo Clinic Scottsdale-Phoenix, Arizona
Rupa S. Kanchi, University of Texas MD Anderson Cancer Center
Bhavani Krishnan, The University of North Carolina at Chapel Hill
David J. Kwaitkowski, Brigham and Women's Hospital
Wembin Lui, University of Texas MD Anderson Cancer Center
Maria J. Merino, National Cancer Institute (NCI)
Gordon B. Mills, University of Texas MD Anderson Cancer Center
Jerome Myers, Centura Health
Michael L. Nickerson, National Cancer Institute (NCI)
Victor E. Reuter, Memorial Sloan-Kettering Cancer Center
Laura S. Schmidt, National Cancer Institute (NCI)
C. Simon Shelley, Leukemia Therapeutics, LLC
Hui Shen, Van Andel Research Institute
Brian Shuch, Yale University
Sabina Signoretti, Dana-Farber Cancer Institute

Document Type

Journal Article

Publication Date

4-3-2018

Journal

Cell Reports

Volume

23

Issue

1

DOI

10.1016/j.celrep.2018.03.075

Keywords

CDKN2A; chromatin remodeling; chromophobe renal cell carcinoma; clear cell renal cell carcinoma; DNA hypermethylation; immune signature; PanCanAtlas; papillary renal cell carcinoma; TCGA

Abstract

© 2018 Renal cell carcinoma (RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD) ChRCC that associated with extremely poor survival. Ricketts et al. find distinctive features of each RCC subtype, providing the foundation for development of subtype-specific therapeutic and management strategies. Somatic alteration of BAP1, PBRM1, and metabolic pathways correlates with subtype-specific decreased survival, while CDKN2A alteration, DNA hypermethylation, and Th2 immune signature correlate with decreased survival within all subtypes.

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