Two single nucleotide polymorphisms in the von Hippel-Lindau tumor suppressor gene in Taiwanese with renal cell carcinoma

BMC Research Notes

Yen-Chein Lai³  Wei-Fang Hsu³  Hui-Ju Chen¹  Mei-Hua Tsou²  Wen-Chung Wang⁴ 

[1] Department of Microbiology and Immunology, Chang Gung University, Taoyuan, Taiwan, Republic of China;Department of Pathology and Laboratory Medicine, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan, Republic of China;School of Medical Laboratory and Biotechnology, Chung Shan Medical University, No.110, Sec. 1, Chien Kuo N. Road, Taichung 402, Taiwan, Republic of China;Department of Obstetrics and Gynecology, Jen-Ai Hospital, Taichung, Taiwan, Republic of China

关键词: Von Hippel-Lindau tumor suppressor gene;    Single nucleotide polymorphism;    Renal cell carcinoma;    Loss of heterozygosity;   

Others  :  1129552
DOI  :  10.1186/1756-0500-7-638

 received in 2013-08-19, accepted in 2014-09-08,  发布年份 2014

【 摘 要 】

Background

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. 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.

Results

Consistent 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.

Conclusions

Our 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.

【 授权许可】

   
2014 Wang et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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