VHL gene mutations and their effects on hypoxia inducible factor HIF{alpha}: Identification of potential driver and passenger mutations

Abstract

Mutations of the von Hippel-Lindau gene (VHL) are frequent in clear cell renal cell carcinomas (ccRCC). Nonsense and frameshift mutations abrogate the function of the VHL protein (pVHL), whereas missense mutations can have different effects. To identify those missense mutations with functional consequences, we sequenced VHL in 256 sporadic ccRCC and identified 187 different VHL mutations of which 65 had missense mutations. Location and destabilizing effects of VHL missense mutations were determined in silico. The majority of thermodyn Show more