Haplotypes, loss of heterozygosity, and expression levels of glycine N-methyltransferase in prostate cancer

Yu Chuen Huang, Cheng Ming Lee, Marcelo Chen, Ming Yi Chung, Yen Hwa Chang, William Ji Shian Huang, Donald Ming Tak Ho, Chin Chen Pan, Tony T. Wu, Stone Yang, Ming Wei Lin, Jer Tsong Hsieh, Yi Ming Arthur Chen

研究成果: 雜誌貢獻文章

43 引文 斯高帕斯(Scopus)

摘要

Purpose: Glycine N-methyltransferase (GNMT) affects genetic stability by regulating DNA methylation and interacting with environmental carcinogens. In a previous study, we showed that GNMT acts as a susceptibility gene for hepatocellular carcinoma. Here, we report on our efforts to characterize the haplotypes, loss of heterozygosity (LOH), and expression levels of the GNMT in prostate cancer. Experimental Design: Peripheral blood mononuclear cell DNA collected from 326 prostate cancer patients and 327 age-matched controls was used to determine GNMT haplotypes. Luciferase reporter constructs were used to compare the promoter activity of different GNMT haplotypes. GNMT LOH rates in tumorous specimens were investigated via a comparison with peripheral blood mononuclear cell genotypes. Immunohistochemical staining was used to analyze GNMT expression in tissue specimens collected from 5 normal individuals, 33 benign prostatic hyperplasia patients, and 45 prostate cancer patients. Results: Three major GNMT haplotypes were identified in 92% of the participants: A, 16GAs/DEL/C (58%); B, 10GAs/INS/C (19.9%); and C, 10GAs/INS/T (14.5%). Haplotype C carriers had significantly lower risk for prostate cancer compared with individuals with haplotype A (odds ratio, 0.68; 95% confidence interval, 0.48-0.95). Results from a phenotypic analysis showed that haplotype C exhibited the highest promoter activity (P < 0.05, ANOVA test). In addition, 36.4% (8 of 22) of the prostatic tumor tissues had LOH of the GNMT gene. Immunohistochemical staining results showed abundant GNMT expression in normal prostatic and benign prostatic hyperplasia tissues, whereas it was diminished in 82.2% (37 of 45) of the prostate cancer tissues. Conclusions: Our findings suggest that GNMT is a tumor susceptibility gene for prostate cancer.
原文英語
頁(從 - 到)1412-1420
頁數9
期刊Clinical Cancer Research
13
發行號5
DOIs
出版狀態已發佈 - 三月 1 2007
對外發佈Yes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Huang, Y. C., Lee, C. M., Chen, M., Chung, M. Y., Chang, Y. H., Huang, W. J. S., Ho, D. M. T., Pan, C. C., Wu, T. T., Yang, S., Lin, M. W., Hsieh, J. T., & Chen, Y. M. A. (2007). Haplotypes, loss of heterozygosity, and expression levels of glycine N-methyltransferase in prostate cancer. Clinical Cancer Research, 13(5), 1412-1420. https://doi.org/10.1158/1078-0432.CCR-06-1551