Biallelic VHL gene inactivation in ccRCC can occur via point mutation, indels (insertion or deletion mutations), loss of alleles on chromosome 3p25 and epigenetic alterations including hypermethylation of the VHL gene promoter resulting in a loss of the tumor suppressor function of pVHL [4,31,32,33,34,35,36]. The gene discussed is VHL; the disease is neoplasm.