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.
Although histologically distinct RCC subtypes exist, emerging themes shared between hereditary and sporadic RCC include dysregulation of the von Hippel-Lindau tumor suppressor protein/hypoxia inducible factor axis, defective ciliogenesis, and aberrant tumor metabolism.
As the identification of novel pVHL targets might provide insights into pVHL tumour suppressor activity, we performed gene expression microarray analysis in VHL-wild-type and VHL-null renal cell carcinoma (RCC) cell lines.
The availability of a RCC cell line from a VHL patient would be useful in studies comparing sporadic RCC with RCC resulting from VHL syndrome; and for determining the relationship or interaction of the RCC gene with the VHL gene to produce a common tumor type.
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.
For an early diagnosis of VHL, before the occurrence of cancers (especially renal cell carcinoma), it is of huge importance to initiate VHL genetic testing in at-risk patients.
These data support the notion of a putative genotoxic effect of TCE leading to VHL gene damage and subsequent occurrence of RCC in highly exposed subjects.
Furthermore, the findings of homozygous inactivation of the VHL gene in a G1 tumor support the notion that the inactivation of the VHL gene is an early event in tumorigenesis of renal cell carcinoma.
Investigation of rare familial forms of renal cell carcinoma (RCC) has led to the identification of genes such as VHL and MET that are also implicated in the pathogenesis of sporadic RCC.
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.