Abstract
BackgroundRenal cell carcinoma, a common malignant tumor arising from the kidney, occurs in 3.62 and 1.95 cases per one hundred thousand people among men and women, respectively, in Taiwan each year. Approximately 80% of cases are classified as clear-cell renal cell carcinoma. Inactivation of the von Hippel-Lindau tumor suppressor gene has been implicated in the tumorigenic pathway of renal cell carcinoma. Two single nucleotide polymorphisms, rs779805 and rs1642742, located in the promoter and 3′ untranslated regions of the von Hippel-Lindau gene are informative and implicated in the occurrence of renal cell carcinoma worldwide. The aim of this study is to clarify whether these polymorphisms are associated with renal cell carcinoma in Taiwanese. Genomic DNA was isolated from normal and tumor tissues of 19 renal cell carcinoma patients. The samples were screened for allelic polymorphisms by restriction fragment length polymorphism with BsaJ I and Acc I digestion. Reconfirmation was carried out by direct sequencing.ResultsConsistent with Knudson’s two-hit theory, AA to AG somatic mutations were observed in rs779805. In addition, loss of heterozygosity in both rs779805 and rs1642742 was demonstrated in 10 out of 15 RCC patients aged 50 or over. The G allele or AG heterozygote frequencies at these two loci were much higher in patient germline DNA when compared with the control group. After adjusting for age, the frequency of the G allele in both loci was much higher for late onset renal cell carcinoma in the Taiwanese population.ConclusionsOur current results confirmed that the existence of G allele in both rs779805 and rs1642742 in the von Hippel-Lindau tumor suppressor gene is of importance in renal cell carcinoma tumorigenesis. However, more comprehensive and detailed research is needed to address the clinical relevance. Larger sample size is required to determine the exact power of correlation between these two genetic polymorphisms and renal cell carcinoma.Electronic supplementary materialThe online version of this article (doi:10.1186/1756-0500-7-638) contains supplementary material, which is available to authorized users.
Highlights
Renal cell carcinoma, a common malignant tumor arising from the kidney, occurs in 3.62 and 1.95 cases per one hundred thousand people among men and women, respectively, in Taiwan each year
In addition to AA to AG somatic mutations, loss of heterozygosity (LOH) was identified in renal cell carcinoma (RCC) patients with AG heterozygote at rs779805 and rs1642742
Polymerase chain reaction (PCR)-Restriction fragment length polymorphism (RFLP) analysis of heterozygotes of A allele and G allele normally results in two equal bands
Summary
A common malignant tumor arising from the kidney, occurs in 3.62 and 1.95 cases per one hundred thousand people among men and women, respectively, in Taiwan each year. Inactivation of the von Hippel-Lindau tumor suppressor gene has been implicated in the tumorigenic pathway of renal cell carcinoma. Rs779805 and rs1642742, located in the promoter and 3′ untranslated regions of the von Hippel-Lindau gene are informative and implicated in the occurrence of renal cell carcinoma worldwide. Von Hippel-Lindau (VHL) disease (OMIM 193300) is an autosomal dominantly inherited tumor syndrome affecting 1 in 36,000 in the human population [1]. The most common types of tumors are retinal angioma, cerebellar and spinal hemangioblastoma, clear cell renal cell carcinoma (RCC) and pheochromocytoma [2]. No studies have focused on the association between VHL gene malfunction and RCC in Taiwan
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