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.
Cell reports. 2018 Apr 03 [Epub]
Christopher J Ricketts, Aguirre A De Cubas, Huihui Fan, Christof C Smith, Martin Lang, Ed Reznik, Reanne Bowlby, Ewan A Gibb, Rehan Akbani, Rameen Beroukhim, Donald P Bottaro, Toni K Choueiri, Richard A Gibbs, Andrew K Godwin, Scott Haake, A Ari Hakimi, Elizabeth P Henske, James J Hsieh, Thai H Ho, Rupa S Kanchi, Bhavani Krishnan, David J Kwaitkowski, Wembin Lui, Maria J Merino, Gordon B Mills, Jerome Myers, Michael L Nickerson, Victor E Reuter, Laura S Schmidt, C Simon Shelley, Hui Shen, Brian Shuch, Sabina Signoretti, Ramaprasad Srinivasan, Pheroze Tamboli, George Thomas, Benjamin G Vincent, Cathy D Vocke, David A Wheeler, Lixing Yang, William T Kim, A Gordon Robertson, Cancer Genome Atlas Research Network , Paul T Spellman, W Kimryn Rathmell, W Marston Linehan
Urologic Oncology Branch, National Cancer Institute, Center for Cancer Research, Bethesda, MD 20892, USA., Vanderbilt University School of Medicine, Nashville, TN 37232, USA., Van Andel Research Institute, Grand Rapids, MI 49503, USA., Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Canada's Michael Smith Genome Sciences Centre, Vancouver, BC V5Z 4S6, Canada., The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., The Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA., Dana-Farber Cancer Institute, Boston, MA 02215, USA., Baylor College of Medicine, Houston, TX 77030, USA., University of Kansas Medical Center, Kansas City, KS 66206, USA., Brigham and Women's Hospital, Boston, MA 02115, USA., Washington University School of Medicine, St. Louis, MO 63110, USA., Mayo Clinic Arizona, Phoenix, AZ 85054, USA., Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA., Centura Health, Centennial, CO 80112, USA., Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA., Urologic Oncology Branch, National Cancer Institute, Center for Cancer Research, Bethesda, MD 20892, USA; Basic Science Program, Leidos Biomedical Research, Inc. Frederick National Laboratory of Cancer Research, Frederick, MD 21702, USA., Leukemia Therapeutics LLC., Hull, MA 02045, USA., Yale University, New Haven, CT 06520, USA., Oregon Health & Science University, Portland, OR 97239, USA., Harvard Medical School, Boston, MA 02115, USA., Urologic Oncology Branch, National Cancer Institute, Center for Cancer Research, Bethesda, MD 20892, USA. Electronic address: .