Aims: The vhl gene is a tumour suppressor gene implicated in renal tumorigenesis in both familial and sporadic renal cell carcinoma (RCC). Alterations in the gene may modify its suppressor function and allow the formation of renal tumours. The purpose of this study was to determine the existence of vhl gene mutations in renal tumour tissue among patients with sporadic RCC and to assess the effects on the structure of the VHL protein.
Materials and methods: This was an observational, analytical and descriptive study of 96 patients who had undergone surgery for sporadic RCC. In surgical specimens of tumour tissue, the three exons of the vhl gene were amplified by polymerase chain reaction and subjected to automatic sequencing. The consequences of the mutations detected on the VHL protein were analysed, taking into account the physical and chemical properties of the amino acids changed by the mutations, the location of the alterations in the protein sequence, the degree of conservation throughout evolution, and prediction of the secondary structure of the protein.
Results: In total, 22 vhl gene mutations were detected in 21 (21.9%) patients; in particular, 13 exonic point mutations consisting of 11 sense mutations, one silent mutation and one missense mutation, plus five exon deletions and one insertion. The remaining three were intronic mutations. All changes occurred in protein functional domains and in regions that have been well conserved throughout evolution. Two-thirds of the intronic mutations were considered relevant for protein function. Among the mutations detected, 72.7% were considered capable of compromising the VHL protein suppressor function.
Conclusions: Mutations in the vhl gene result in amino acid changes in the protein that usually occur at important functional sites that have been conserved throughout evolution and where the binding domains for other proteins are located and exert their suppressor function.