Significance of VHL changes in sporadic renal cell carcinoma

The von Hippel-Lindau (VHL) tumour suppressor gene is central to the development of sporadic conventional clear cell renal cell carcinoma (ccRCC). The role VHL plays as part of a ubiquitin ligase targeting HIF-a for proteasomal degradation underpins many changes seen in ccRCC but the importance of other VHL functions and the clinical significance of specific genetic/epigenetic changes are not clear. Genetic and epigenetic analysis of VHL gene in 86 tumours from patients with ccRCC was carried out, adding to the 96 tumours already analysed in an ongoing study within the group. Overall, loss of heterozygosity (LOH) was found in 89.2%, mutation in 74.6% and methylation in 30.9%. Evidence of biallelic inactivation (LOH and mutation or methylation alone) was "found in 84.9% whilst no involvement of VHL was found in only 4% of samples, consistent with VHL involvement in the majority of conventional ccRCCs. Associations between mutation and gender (p=0.0189), LOH and grade (p=0.0097) and methylation and grade (p=0.0159) were found with a possible association between methylation and gender (p=0.0835). There was a suggestion of LOH and mutation correlating with a better overall survival compared to patients with no VHL involvement and a similar relationship was seen with methylation; however sample numbers were small in the no VHL group and neither reached statistical significance.EThOS - Electronic Theses Online ServiceGBUnited Kingdo