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

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...

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Autores principales: Wang, Wen-Chung, Tsou, Mei-Hua, Chen, Hui-Ju, Hsu, Wei-Fang, Lai, Yen-Chein
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4168206/
https://www.ncbi.nlm.nih.gov/pubmed/25217002
http://dx.doi.org/10.1186/1756-0500-7-638
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author Wang, Wen-Chung
Tsou, Mei-Hua
Chen, Hui-Ju
Hsu, Wei-Fang
Lai, Yen-Chein
author_facet Wang, Wen-Chung
Tsou, Mei-Hua
Chen, Hui-Ju
Hsu, Wei-Fang
Lai, Yen-Chein
author_sort Wang, Wen-Chung
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1756-0500-7-638) contains supplementary material, which is available to authorized users.
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spelling pubmed-41682062014-09-20 Two single nucleotide polymorphisms in the von Hippel-Lindau tumor suppressor gene in Taiwanese with renal cell carcinoma Wang, Wen-Chung Tsou, Mei-Hua Chen, Hui-Ju Hsu, Wei-Fang Lai, Yen-Chein BMC Res Notes Research Article 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1756-0500-7-638) contains supplementary material, which is available to authorized users. BioMed Central 2014-09-12 /pmc/articles/PMC4168206/ /pubmed/25217002 http://dx.doi.org/10.1186/1756-0500-7-638 Text en © Wang et al.; licensee BioMed Central Ltd. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated
spellingShingle Research Article
Wang, Wen-Chung
Tsou, Mei-Hua
Chen, Hui-Ju
Hsu, Wei-Fang
Lai, Yen-Chein
Two single nucleotide polymorphisms in the von Hippel-Lindau tumor suppressor gene in Taiwanese with renal cell carcinoma
title Two single nucleotide polymorphisms in the von Hippel-Lindau tumor suppressor gene in Taiwanese with renal cell carcinoma
title_full Two single nucleotide polymorphisms in the von Hippel-Lindau tumor suppressor gene in Taiwanese with renal cell carcinoma
title_fullStr Two single nucleotide polymorphisms in the von Hippel-Lindau tumor suppressor gene in Taiwanese with renal cell carcinoma
title_full_unstemmed Two single nucleotide polymorphisms in the von Hippel-Lindau tumor suppressor gene in Taiwanese with renal cell carcinoma
title_short Two single nucleotide polymorphisms in the von Hippel-Lindau tumor suppressor gene in Taiwanese with renal cell carcinoma
title_sort two single nucleotide polymorphisms in the von hippel-lindau tumor suppressor gene in taiwanese with renal cell carcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4168206/
https://www.ncbi.nlm.nih.gov/pubmed/25217002
http://dx.doi.org/10.1186/1756-0500-7-638
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