TY - JOUR
T1 - The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma
AU - The Cancer Genome Atlas Research Network
AU - Ricketts, Christopher J.
AU - De Cubas, Aguirre A.
AU - Fan, Huihui
AU - Smith, Christof C.
AU - Lang, Martin
AU - Reznik, Ed
AU - Akbani, Rehan
AU - Kanchi, Rupa S.
AU - Mills, Gordon B.
AU - Tamboli, Pheroze
AU - Liu, Yuexin
AU - Zhang, Wei
AU - Broom, Bradley M.
AU - Ju, Zhenlin
AU - Korkut, Anil
AU - Li, Jun
AU - Liang, Han
AU - Ling, Shiyun
AU - Liu, Wenbin
AU - Lu, Yiling
AU - Rao, Arvind
AU - Weinstein, John N.
AU - Zhang, Jiexin
AU - Liu, Xiuping
AU - Wang, Linghua
AU - Carvalho, Andre L.
AU - Fregnani, José H.
AU - Reis, Rui M.
AU - Scapulatempo-Neto, Cristovam
AU - Ajani, Jaffer A.
AU - Behrens, Carmen
AU - Bondaruk, Jolanta
AU - Broaddus, Russell
AU - Czerniak, Bogdan
AU - Esmaeli, Bita
AU - Fujimoto, Junya
AU - Gershenwald, Jeffrey
AU - Guo, Charles
AU - Lazar, Alexander J.
AU - Logothetis, Christopher
AU - Meric-Bernstam, Funda
AU - Moran, Cesar
AU - Ramondetta, Lois
AU - Rice, David
AU - Sood, Anil
AU - Thompson, Timothy
AU - Troncoso, Patricia
AU - Tsao, Anne
AU - Wistuba, Ignacio
AU - von Deimling, Andreas
N1 - Publisher Copyright:
© 2018
PY - 2018/4/3
Y1 - 2018/4/3
N2 - 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.
AB - 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.
KW - CDKN2A
KW - DNA hypermethylation
KW - PanCanAtlas
KW - TCGA
KW - chromatin remodeling
KW - chromophobe renal cell carcinoma
KW - clear cell renal cell carcinoma
KW - immune signature
KW - papillary renal cell carcinoma
UR - http://www.scopus.com/inward/record.url?scp=85044860979&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85044860979&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2018.03.075
DO - 10.1016/j.celrep.2018.03.075
M3 - Article
C2 - 29617669
AN - SCOPUS:85044860979
SN - 2211-1247
VL - 23
SP - 313-326.e5
JO - Cell Reports
JF - Cell Reports
IS - 1
ER -