The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

The Cancer Genome Atlas Research Network

Research output: Contribution to journalArticle

57 Citations (Scopus)

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. 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.

Original languageEnglish (US)
Pages (from-to)313-326.e5
JournalCell Reports
Volume23
Issue number1
DOIs
StatePublished - Apr 3 2018

Fingerprint

Atlases
Renal Cell Carcinoma
Genes
Cells
Genome
DNA
Gene expression
Neoplasms
Survival
Metabolic Networks and Pathways
Transcriptome
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma. / The Cancer Genome Atlas Research Network.

In: Cell Reports, Vol. 23, No. 1, 03.04.2018, p. 313-326.e5.

Research output: Contribution to journalArticle

The Cancer Genome Atlas Research Network. / The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma. In: Cell Reports. 2018 ; Vol. 23, No. 1. pp. 313-326.e5.
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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. 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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