DNA mismatch repair gene methylation in gastric cancer in individuals from northern Brazil.

E. Moura Lima, M. Ferreira Leal, M. C. Cardoso Smith, R. R. Rodriguez Burbano, P. Pimentel de Assumpção, M. J. Bello, J. Rey, Francinaldo Ferreira de Lima, C. Casartelli
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引用次数: 27

Abstract

Gastric cancer is one of the most common malignancies. DNA methylation is implicated in DNA mismatch repair genes deficiency. In the present study, we evaluated the methylation status of MLH1, MSH2, MSH6 and PMS2 in 20 diffuse- and 26 intestinal-type gastric cancer samples and 20 normal gastric mucosal of gastric cancer patients from Northern Brazil. We found that none of the nonneoplastic samples showed methylation of any gene promoter and 50% of gastric cancer samples showed at least one methylated gene promoter. Methylation frequencies of MLH1, MSH2, MSH6 and PMS2 promoter were 21.74%, 17.39%, 0% and 28.26% respectively in gastric cancer samples. MLH1 and PMS2 methylation were associated with neoplastic samples compared to nonneoplastic ones. PMS2 methylation was associated with diffuse- and intestinal-type cancer compared with normal controls. Intestinal-type cancer showed significant association with MLH1 methylation. Diffuse-type cancer was significantly associated with MSH2 methylation. Our findings show differential gene methylation in tumoral tissue, which allows us to conclude that methylation is associated with gastric carcinogenesis. Methylation of mismatch repair genes was associated with gastric carcinogenesis and may be a helpful tool for diagnosis, prognosis and therapies. However, MSH6 does not seem to be regulated by methylation in our samples.
巴西北部个体胃癌DNA错配修复基因甲基化。
胃癌是最常见的恶性肿瘤之一。DNA甲基化与DNA错配修复基因缺陷有关。在本研究中,我们评估了来自巴西北部胃癌患者的20例弥漫性胃癌和26例肠型胃癌样本以及20例正常胃粘膜中MLH1、MSH2、MSH6和PMS2的甲基化状态。我们发现,没有任何非肿瘤样本显示任何基因启动子甲基化,50%的胃癌样本显示至少一个甲基化的基因启动子。胃癌样本中MLH1、MSH2、MSH6和PMS2启动子甲基化频率分别为21.74%、17.39%、0%和28.26%。与非肿瘤样品相比,MLH1和PMS2甲基化与肿瘤样品相关。与正常对照相比,PMS2甲基化与弥漫性癌和肠型癌相关。肠型癌与MLH1甲基化显著相关。弥漫性癌与MSH2甲基化显著相关。我们的研究结果显示肿瘤组织中存在差异基因甲基化,这使我们能够得出甲基化与胃癌发生有关的结论。错配修复基因的甲基化与胃癌的发生有关,可能是诊断、预后和治疗的有用工具。然而,在我们的样本中,MSH6似乎不受甲基化的调节。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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