Genetic and epigenetic alterations in the von hippel-lindau gene: the influence on renal cancer prognosis.
نویسندگان
چکیده
BACKGROUND Inactivation of the von Hippel-Lindau (VHL) gene is considered as an early event in renal cancer tumorigenesis. The prognostic relevance of these changes, however, is not clear and previous results are contradictory. We have evaluated the influence of (epi)genetic alterations in VHL on cause-specific survival in clear-cell renal cell cancer (ccRCC) in a large, population-based group of cases. METHODS One hundred and eighty-five cases of ccRCC, identified in the Netherlands Cohort Study on diet and cancer diagnosed in the period 1986 to 1997, were included in the analyses. Mortality information until December 2005, including causes of death, were obtained for all cases through linkage with the Central Bureau of Statistics. VHL mutations were determined with PCR single-strand conformational polymorphism and direct sequencing. VHL methylation was determined with methylation-specific PCR. Kaplan-Meier analyses and Cox proportional hazards models were used to assess associations between VHL alterations and cause-specific mortality. RESULTS Median follow-up in our population was 6 years. The frequency of loss of function mutations and methylation, separately or combined, did not differ statistically significant between different cancer stages or between tumors with different sizes. We observed no influence of loss of function mutations or methylation of the VHL gene on cause-specific mortality (hazard ratio, 1.08; 95% confidence interval, 0.69-1.68, P = 0.735) as compared with patients with a wild-type or silent mutation in VHL. DISCUSSION Our results indicate that (epi)genetic alterations in the VHL gene do not have prognostic value in ccRCC.
منابع مشابه
Von Hippel-Lindau (VHL) Inactivation in Sporadic Clear Cell Renal Cancer: Associations with Germline VHL Polymorphisms and Etiologic Risk Factors
Renal tumor heterogeneity studies have utilized the von Hippel-Lindau VHL gene to classify disease into molecularly defined subtypes to examine associations with etiologic risk factors and prognosis. The aim of this study was to provide a comprehensive analysis of VHL inactivation in clear cell renal tumors (ccRCC) and to evaluate relationships between VHL inactivation subgroups with renal canc...
متن کاملImproved identification of von Hippel-Lindau gene alterations in clear cell renal tumors.
PURPOSE To provide a comprehensive, thorough analysis of somatic mutation and promoter hypermethylation of the von Hippel-Lindau (VHL) gene in the cancer genome, unique to clear cell renal cancer (ccRCC). Identify relationships between the prevalence of VHL gene alterations and alteration subtypes with patient and tumor characteristics. EXPERIMENTAL DESIGN As part of a large kidney cancer cas...
متن کاملUnusual diagnosis of Von Hippel Lindau syndrome on PET/CT - Case report and brief review of literature
We report an unusual case of a young male with cerebellar hemangioblastoma treated previously for medullary carcinoma of thyroid, whose PET/CT scans revealed a constellation of findings that suggested the rare Von Hippel Lindau syndrome. The diagnosis was clinched by confirming the findings on whole body contrast enhanced computed tomography (CECT) and contrast enha...
متن کاملRenal Cell Carcinoma in von Hippel–Lindau Disease—From Tumor Genetics to Novel Therapeutic Strategies
von Hippel-Lindau (VHL) disease is an autosomal dominant syndrome caused by mutations in the VHL tumor-suppressor gene, leading to the dysregulation of many hypoxia-induced genes. Affected individuals are at increased risk of developing recurrent and bilateral kidney cysts and dysplastic lesions which may progress to clear cell renal cell carcinoma (ccRCC). Following the eponymous VHL gene inac...
متن کاملDifferent Angiogenic Potential in Low and High Grade Sporadic Clear Cell Renal Cell Carcinoma Is Not Related to Alterations in the von Hippel–Lindau Gene
BACKGROUND von Hippel-Lindau (VHL) inactivation is common in sporadic clear cell renal cell carcinomas (ccRCC). pVHL is part of the ubiquitin ligase complex that targets the alpha subunits of hypoxia-inducible transcription factor (HIF) for degradation under well-oxygenated conditions. In the absence of wild-type pVHL, as observed in VHL patients and most sporadic ccRCCs, constitutive upregulat...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Clinical cancer research : an official journal of the American Association for Cancer Research
دوره 14 3 شماره
صفحات -
تاریخ انتشار 2008