The Cancer Genome Atlas comprehensive molecular characterization of renal cell carcinoma Journal Article

   


Authors: 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.; The Cancer Genome Atlas Research Network; Spellman, P. T.; Rathmell, W. K.; Linehan, W. M.
Article Title: The Cancer Genome Atlas comprehensive molecular characterization of renal cell carcinoma
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. © 2018
Keywords: human tissue; gene mutation; major clinical study; cancer staging; phenotype; gene expression; genetic association; dna methylation; renal cell carcinoma; cancer genetics; genome analysis; cancer specific survival; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; clinical evaluation; cyclin dependent kinase inhibitor 2a; gene dosage; immune response gene; tumor gene; cdkn2a; clear cell renal cell carcinoma; dna hypermethylation; bap1 gene; papillary renal cell carcinoma; tcga; chromophobe renal cell carcinoma; chromatin remodeling; pbrm1 gene; human; priority journal; article; pancanatlas; immune signature; th2 gene
Journal Title: Cell Reports
Volume: 23
Issue: 1
ISSN: 2211-1247
Publisher: Cell Press  
Date Published: 2018-04-03
Start Page: 313
End Page: 326.e5
Language: English
DOI: 10.1016/j.celrep.2018.03.075
PROVIDER: scopus
PUBMED: 29617669
PMCID: PMC6075733
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85044860979&doi=10.1016%2fj.celrep.2018.03.075&partnerID=40&md5=42da773b855998246e5666bc63dd028e
Notes: Article -- Export Date: 1 May 2018 -- Source: Scopus
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MSK Authors
  1. Victor Reuter
    1228 Reuter
  2. Abraham Ari Hakimi
    324 Hakimi
  3. Eduard Reznik
    103 Reznik
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