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The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma
Journal article   Open access   Peer reviewed

The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

Christopher J Ricketts, Aguirre A De Cubas, Huihui Fan, Christof C Smith, Martin Lang, Ed Reznik, Reanne Bowlby, Ewan A Gibb, Rehan Akbani, Rameen Beroukhim, …
Cell reports (Cambridge), Vol.23(1), pp.313-326.e5
04/03/2018
DOI: 10.1016/j.celrep.2018.03.075
PMCID: PMC6075733
PMID: 29617669
url
https://doi.org/10.1016/j.celrep.2018.03.075View
Published (Version of record) Open Access

Abstract

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.
Phenotype Biomarkers, Tumor - genetics Biomarkers, Tumor - immunology Biomarkers, Tumor - metabolism Carcinoma, Renal Cell - genetics Carcinoma, Renal Cell - metabolism Carcinoma, Renal Cell - pathology Cyclin-Dependent Kinase Inhibitor p16 - genetics Cyclin-Dependent Kinase Inhibitor p16 - metabolism DNA-Binding Proteins Genome, Human Humans Kidney Neoplasms - genetics Kidney Neoplasms - metabolism Kidney Neoplasms - pathology Metabolic Networks and Pathways Nuclear Proteins - genetics Nuclear Proteins - metabolism PTEN Phosphohydrolase - genetics PTEN Phosphohydrolase - metabolism Survival Analysis Transcription Factors - genetics Transcription Factors - metabolism Tumor Suppressor Proteins - genetics Ubiquitin Thiolesterase - genetics

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