This association of a proposed occupational cause and occurrence of renal-cell carcinoma emphasizes the availability and use of VHL sequencing for both studying the pathophysiology of malignant transformation and potentially playing a clinical role in genetic counseling or risk assessment.
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.
Role of transforming growth factor-alpha in von Hippel--Lindau (VHL)(-/-) clear cell renal carcinoma cell proliferation: a possible mechanism coupling VHL tumor suppressor inactivation and tumorigenesis.
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.
By comparison to much lower reported VHL mutation frequencies of 33-55% in TRI-unexposed RCC patients, these results indicate a specifically high mutation frequency at the VHL gene in TRI-exposed RCC patients; four of these aberrations have thus far been confirmed as VHL mutations by sequence analysis.