Chromophobe cell

Clear cell

Cancer research

Biology

Cancer

CDKN2A

Internal medicine

Pathology

Papillary renal cell carcinomas

Renal cell carcinoma

Clear cell renal cell carcinoma

Oncology

Medicine

Nature Reviews Urology

The Cancer Genome Atlas (TCGA) characterized the somatic genetic and genomic alterations in renal cell carcinoma (RCC) encompassing the major RCC histological subtypes, including clear cell RCC (ccRCC), papillary RCC (pRCC) and chromophobe RCC (chRCC). Unique distinguishing features were found between the RCC subtypes, including in chromosomal alterations and tumour metabolism, as well as within each RCC subtype, of which some correlated with differences in patient survival. Two new RCC subtypes were defined by distinct epigenetic and metabolic pathway expression patterns, the hypermethylated CpG island methylator phenotype-associated (CIMP) RCCs and metabolically divergent chRCCs, and new biomarkers of poor patient outcome were identified, including PBRM1 mutation in type 1 pRCC and CDKN2A loss in chRCC. Expression of many immune cell gene-specific signatures was increased in ccRCC compared with pRCC and chRCC, and expression of select signatures, including the type 2 T helper cell signature, was increased in CIMP RCC. Increased expression of the type 2 T helper cell signature correlated with poorer survival in ccRCC, pRCC and chRCC. In addition to improving our current understanding of RCC, TCGA RCC studies are an invaluable resource that provides the foundation for the development of improved methods for diagnosis, treatment and prevention of this disease. This Review by Ricketts and Linehan comprehensively summarizes the findings of The Cancer Genome Atlas analyses of renal cell carcinoma and their clinical implications. The authors highlight unique and shared features of the tumour histological subtypes, their predictive power and their possible utility as therapeutic targets.

The Cancer Genome Atlas of renal cell carcinoma: findings and clinical implications