The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

• Published in: Cell reports (Cambridge) Vol. 23; no. 1; pp. 313 - 326.e5
• Main Authors: Reznik, Ed, Reuter, Victor E., Signoretti, Sabina, Srinivasan, Ramaprasad, Wheeler, David A., Yang, Lixing, Kim, William Y., Robertson, A. Gordon, Zhang, Jiashan (Julia), Wu, Ye, Liu, Yuexin, Kanchi, Rupa S., Zhang, Jiexin, Gross, Benjamin E., Kundra, Ritika, Phillips, Sarah M., Zhang, Hongxin, Peto, Myron, Mungall, Andrew J., Lai, Phillip H., Van Den Berg, David J., Bodenheimer, Tom, Simons, Janae V., Veluvolu, Umadevi, Fan, Huihui, Bellair, Michelle, Dinh, Huyen, Doddapaneni, HarshaVardhan, Han, Yi, Lee, Sandra, Li, Wei, Mardis, Elaine R., Gastier-Foster, Julie M., Lichtenberg, Tara M., Le, Xuan, Thorp, Richard, Lyadov, Vladimir, De Rose, Agostino, Rabeno, Brenda, Têtu, Bernard, Chabot, John, Hibshoosh, Hanina, Potapova, Olga, Mariani, Odette, Bigner, Darell, Stoop, Hans, Cuppini, Lucia, Finocchiaro, Gaetano, Murawa, Dawid, Guillermo, Armando López, Van Bang, Nguyen, Akeredolu, Teniola, Birrer, Michael, Nagorney, David, Stanton, Melissa, Yang, Ju Dong, Bondaruk, Jolanta, Broaddus, Russell, Guo, Charles, Lazar, Alexander J., Meric-Bernstam, Funda, Tsao, Anne, Carter, Candace, Haydu, Lauren, Hersey, Peter, Synott, Maria, Drwiega, Paul, Hung, Nguyen Phi, Kebebew, Electron, Metwalli, Adam R., Schmidt, Laura S., Cernat, Mircea, Gorincioi, Ghenadie, Tamakawa, Raina, Chevalier, Simone, McKercher, Ginette, Smolenski, Kathy, Alvaro, Domenico, Bragazzi, Maria Consiglia, Cardinale, Vincenzo, Chesla, David, Cottingham, Sandra, Lehman, Norman L., Powers, James, Huland, Hartwig, Sauter, Guido, Carroll, Peter R., Forgie, Ian, Carney, Michael, Knutson, Tina, Godwin, Andrew K., Boussioutas, Alex, Saad, Fred, Bocklage, Therese, Feldman, Michael, Valdivieso, Federico, Dhir, Rajiv, Sankarankuty, Ajith, Fantacone-Campbell, J. Leigh, Rubin, Mark A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03.04.2018; Elsevier
• Subjects: Biomarkers, Tumor - genetics; Biomarkers, Tumor - immunology; Biomarkers, Tumor - metabolism; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - metabolism; Carcinoma, Renal Cell - pathology; CDKN2A; chromatin remodeling; chromophobe renal cell carcinoma; clear cell renal cell carcinoma; Cyclin-Dependent Kinase Inhibitor p16 - genetics; Cyclin-Dependent Kinase Inhibitor p16 - metabolism; DNA hypermethylation; DNA-Binding Proteins; Genome, Human; Humans; immune signature; Kidney Neoplasms - genetics; Kidney Neoplasms - metabolism; Kidney Neoplasms - pathology; Metabolic Networks and Pathways; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; PanCanAtlas; papillary renal cell carcinoma; Phenotype; PTEN Phosphohydrolase - genetics; PTEN Phosphohydrolase - metabolism; Survival Analysis; TCGA; Transcription Factors - genetics; Transcription Factors - metabolism; Tumor Suppressor Proteins - genetics; Ubiquitin Thiolesterase - genetics; clear cell renal cell carcinoma; papillary renal cell carcinoma; chromophobe renal cell carcinoma; CDKN2A; PanCanAtlas; immune signature; chromatin remodeling; DNA hypermethylation; TCGA
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2018.03.075

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. [Display omitted] •BAP1, PBRM1, and metabolic pathway changes correlate with RCC subtype-specific survival•DNA hypermethylation/CDKN2A alterations associate with poor survival in all RCC subtypes•Immune gene signatures increased in ccRCC and CIMP-RCC•Increased Th2 gene signature within each RCC subtype associates with poorer 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.