MUTATIONS OF THE VHL TUMOR-SUPPRESSOR GENE IN RENAL-CARCINOMA

Multiple, bilateral renal carcinomas are a frequent occurrence in von Hippel-Lindau (VHL) disease. To elucidate the aetiological role of the VHL gene in human kidney tumorigenesis, localized and advanced tumour s from 110 patients with sporadic renal carcinoma were analysed for VH L mutations and loss of heterozygosity (LOH). VHL mutations were ident ified in 57% of clear cell renal carcinomas analysed and LOH was obser ved in 98% of those samples. Moreover, VHL was mutated and lost in a r enal tumour from a patient with familial renal carcinoma carrying the constitutional translocation, t(3;8)(p14;q24). The identification of V HL mutations in a majority of localized and advanced sporadic renal ca rcinomas and in a second form of hereditary renal carcinoma indicates that the VHL gene plays a critical part in the origin of this malignan cy.