Although CA XII expression levels tended to be lower in RCC cell lines without the VHL mutation and in transformants of the wild-type VHL gene, the results were not conclusive.
The von Hippel-Lindau (VHL) gene is often inactivated (by mutation or promoter hypermethylation) in renal cell carcinoma but the relation to therapeutic outcome is unclear.
Thus, these results strongly suggest that the expression of HGF/SF and Met protein is closely associated with the genetic alterations of VHL and HGF/SF in primary RCCs.
Mutations in the von Hippel-Lindau (VHL) gene are involved in the family cancer syndrome for which it is named and the development of sporadic renal cell cancer (RCC).
HIFs contribute to the pathogenesis of many cancers, particularly the clear cell type of renal cell carcinoma in which loss of function of the von Hippel-Lindau tumor suppressor blocks HIF-2α degradation.
Among the 11 non-responders 7 (64%) were wild-type, 2 (18%) were p53 mutated and 2 (18%) VHL1 mutated.No significant associations were found among RCC histotype, mutation variants and response to therapies.
Amplification of DNA from selected cell populations was demonstrated by detecting a loss of heterozygosity (LOH) at the von Hippel-Lindau disease (VHL) gene in an atypical renal lesion and a renal cell carcinoma in a kidney of a VHL patient.
Elevated number of circulating EPCs seems to be related to high EPO production from RCC with novel double somatic mutation of the VHL gene in this patient.
Tumor-specific intragenic VHL pathogenic mutations were detected in 38% (11/29) of the ccRCC patients and 33% (2/6) of the patients with other types of RCC.
Large VHL gene deletions associated with a contiguous loss of C3orf10 were associated with a significantly lower lifetime risk of RCC than deletions that did not involve C3orf10.
Studies of the tricarboxylic acid cycle and the VHL-HIF pathways have provided the foundation for therapeutic approaches in patients with HLRCC-associated kidney cancer as well as other hereditary and sporadic forms of RCC.
We investigated whether TRI exposure produces RCC through a specific mutational effect on the VHL gene by analyzing VHL sequences in the RCCs of patients exposed to high, cumulative doses of TRI.
Our findings suggest that the risk of RCC in VHL is attributable to the severity of the amino acid substitution at this particular codon in the VHL protein.
Association of GSTT1 non-null and NAT1 slow/rapid genotypes with von Hippel-Lindau tumour suppressor gene transversions in sporadic renal cell carcinoma.
The von Hippel-Lindau tumor suppressor gene (VHL) is mutated in clear cell renal cell carcinomas (RCC), leading to the activation of hypoxia-inducible factor (HIF)-mediated gene transcription.
These results indicate that VHL gene mutations are related to the carcinogenesis of the clear-cell type of primary renal cell carcinomas, whereas alteration of the APC gene is not involved in the pathogenesis of this cancer.
Mutation of the von Hippel-Lindau (VHL) gene is responsible for familial and sporadic renal cell carcinomas as well as for cancers in many other organs.