VHL and neoplasm: Biallelic inactivation of the von Hippel–Lindau (VHL) tumour suppressor gene is a truncal genetic event that arises in the majority of cases of ccRCC3–6, demonstrating that loss of one or more of the various tumour suppressor functions of the pVHL protein isoforms2,7 is central to the earliest steps in the initiation of tumour formation.