The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma
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Publication date
2018-04-03
Authors
Ricketts, Christopher J.
De Cubas, Aguirre A.
Fan, Huihui
Smith, Christof C.
Lang, Martin
Reznik, Ed
Bowlby, Reanne
Gibb, Ewan A.
Akbani, Rehan
Beroukhim, Rameen
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Article
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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.
Keywords
CDKN2A, chromatin remodeling, chromophobe renal cell carcinoma, clear cell renal cell carcinoma, DNA hypermethylation, immune signature, PanCanAtlas, papillary renal cell carcinoma, TCGA, General Biochemistry,Genetics and Molecular Biology
Citation
Ricketts, C J, De Cubas, A A, Fan, H, Smith, C C, Lang, M, Reznik, E, Bowlby, R, Gibb, E A, Akbani, R, Beroukhim, R, Bottaro, D P, Choueiri, T K, Gibbs, R A, Godwin, A K, Haake, S, Hakimi, A A, Henske, E P, Hsieh, J J, Ho, T H, Kanchi, R S, Krishnan, B, Kwaitkowski, D J, Lui, W, Merino, M J, Mills, G B, Myers, J, Nickerson, M L, Reuter, V E, Schmidt, L S, Shelley, C S, Shen, H, Shuch, B, Signoretti, S, Srinivasan, R, Tamboli, P, Thomas, G, Vincent, B G, Vocke, C D, Wheeler, D A, Yang, L, Kim, W T, Robertson, A G, Caesar-Johnson, S J, Demchok, J A, Felau, I, Kasapi, M, Ferguson, M L, Hutter, C M, Zhang, J, de Krijger, R & The Cancer Genome Atlas Research Network 2018, 'The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma', Cell Reports, vol. 23, no. 1, pp. 313-326.e5. https://doi.org/10.1016/j.celrep.2018.03.075