Figure 1.

Kidney cancer is not a single disease; it is made up of a number of cancers that occur in the kidney, each with a distinct histology, each with a different clinical course, each responding differently to therapy, and each caused by a different gene. The VHL gene is mutated in the germline of ∼100% of von Hippel-Lindau families and the majority of sporadic clear cell RCCs. The MET gene is mutated in the germline of ∼100% of hereditary papillary renal carcinoma families and is mutated in a subset of tumors (13%) from patients with sporadic, type 1 papillary kidney cancer. The fumarate hydratase gene (FH) is the gene for the inherited form of type 2 papillary kidney cancer associated with hereditary leiomyomatosis renal cell carcinoma (HLRCC). Sporadic papillary type 2 RCC is composed of a mixture of kidney cancers including collecting duct and medullary RCC. The gene(s) for sporadic type 2 papillary RCC, collecting duct RCC, and medullary RCC is not known. The FLCN is mutated in 96% of families affected with the inherited form of chromophobe RCC and oncocytoma associated with Birt-Hogg-Dubé syndrome. The genes for the sporadic forms of chromophobe RCC and oncocytoma are not known. TFE3, TFEB, and MITF are part of the MiT family of transcription factors. TFE3 and TFEB translocation kidney cancer are sporadic (nonhereditary); germline mutations of MITF have been found in the germline of patients with melanoma and kidney cancer or both. (Fig. 1 adapted from Linehan et al. 2003.)