Michailidi Christina, Theocharis Stamatios, Tsourouflis Gerasimos, Pletsa Vasiliki, Kouraklis Gregorios, Patsouris Efstratios, Papavassiliou Athanasios G, Troungos Constantinos
Department of Biological Chemistry, University of Athens Medical School, Athens 11527, Greece.
First Department of Pathology, University of Athens Medical School, Athens 11527, Greece.
Exp Biol Med (Maywood). 2015 Dec;240(12):1599-605. doi: 10.1177/1535370215583800. Epub 2015 Apr 23.
Colorectal cancer (CRC) is the third most common cancer in men and the second in women worldwide. CRC development is the result of genetic and epigenetic alterations accumulation in the epithelial cells of colon mucosa. In the present study, DNA methylation, an epigenetic event, was evaluated in tumoral and matching normal epithelium in a cohort of 61 CRC patients. The results confirmed and expanded knowledge for the tumor suppressor genes hMLH1, MGMT, APC, and CDH1. Promoter methylation was observed for all the examined genes in different percentage. A total of 71% and 10% of the examined cases were found to be methylated in two or more and in all genes, respectively. mRNA and protein levels were also evaluated. Promoter methylation of hMLH1, MGMT, APC, and CDH1 genes was present at the early stages of tumor's formation and it could also be detected in the normal mucosa. Correlations of the methylated genes with patient's age and tumor's clinicopathological characteristics were also observed. Our findings suggest that DNA methylation is a useful marker for tumor progression monitoring and that promoter methylation in certain genes is associated with more advanced tumor stage, poor differentiation, and metastasis.
结直肠癌（CRC）是全球男性中第三大常见癌症，女性中第二大常见癌症。CRC的发生是结肠黏膜上皮细胞中遗传和表观遗传改变积累的结果。在本研究中，对61例CRC患者队列中的肿瘤组织及配对的正常上皮组织进行了DNA甲基化（一种表观遗传事件）评估。结果证实并扩展了对肿瘤抑制基因hMLH1、MGMT、APC和CDH1的认识。所有检测基因均观察到不同比例的启动子甲基化。分别有71%和10%的检测病例在两个或更多基因以及所有基因中发生甲基化。还评估了mRNA和蛋白质水平。hMLH1、MGMT、APC和CDH1基因的启动子甲基化在肿瘤形成的早期阶段就已存在，并且在正常黏膜中也可检测到。还观察到甲基化基因与患者年龄和肿瘤临床病理特征之间的相关性。我们的研究结果表明，DNA甲基化是监测肿瘤进展的有用标志物，某些基因的启动子甲基化与更晚期的肿瘤阶段、低分化和转移相关。
