The central role of VHL in ccRC is supported by animal models that show the formation of renal cysts in animals with a loss of one VHL allele while those with biallelic loss develop RCC tumors [7], and by molecular analysis of multiple primary and metastatic samples that show that VHL loss is a clonal and early event in ccRC carcinogenesis [8]. This evidence concerns the gene VHL and renal cell carcinoma.