Renal cell carcinoma (RCC) refers to various neoplasms of renal origin. The four major histological subtypes are conventional (clear cell RCC), papillary, chromophobic, and collecting duct. Four genes have been well studied in the hereditary form of renal carcinoma. These are von Hippel-Lindau(VHL), MET, fumarate hydratase (FH) and Birt Hogg Dube (BHD).VHL associated tumors are clear cell carcinomas. Mutations in the VHL gene prevent the ubiquitination of HIF-1α leading to its accumulation. This results in the production of growth factors that enhance angiogenesis and cell growth. Mutations in the FH gene cause hereditary leiomyomatosis and renal cancer syndrome papillary renal tumors. Mutations in FH also lead to accumulation of fumarate in the cell eventually preventing VHL-mediated degradation of HIF-alpha.
The oncogene MET has also been implicated in hereditary papillary renal cancer. Activating mutations in the tyrosine kinase domain of MET lead to changes in cell motility, cellular transformation, prevention of apoptosis and metastasis. BHD is a novel tumor supressor gene whose function in normal cells and role in RCC is yet to be determined.