胶质瘤中MGMT和hMLH1甲基化与表达水平的变化及意义

首都医科大学学报 ›› 2009, Vol. 30 ›› Issue (2): 203-207.

胶质瘤中MGMT和hMLH1甲基化与表达水平的变化及意义

陈慧媛¹, 江涛², 袁芳¹, 崔云¹, 李桂林¹, 黄磊²

1. 首都医科大学附属北京市神经外科研究所神经病理室;2. 首都医科大学附属北京天坛医院神经外科脑胶质瘤诊治中心

收稿日期:2008-10-17 修回日期:1900-01-01 出版日期:2009-04-21 发布日期:2009-04-21
通讯作者: 李桂林

The Methylation Status and Expression of MGMT and hMLH1 in Glioma and Their Clinical Significance

CHEN Hui-yuan¹, JIANG Tao², Yuan Fang¹, CUI Yun¹, LI Gui-lin¹, HUANG Lei²

1. Department of Neuropathology, Beijing Neurosurgical Institute, Capital Medical University;2. Glioma Center in Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University

Received:2008-10-17 Revised:1900-01-01 Online:2009-04-21 Published:2009-04-21

摘要/Abstract

摘要： 目的探讨胶质瘤组织中,O⁶-甲基鸟嘌呤-DNA甲基转移酶(O⁶-methylguanine DNA methyltransferase,MGMT)和错配修复基因mutL homolog 1(Homo sapiens,hMLH1)的甲基化及蛋白水平的变化,及其在胶质瘤发生中的作用。方法应用甲基化特异性PCR(methylation-specific PCR,MSP) 方法检测了78例胶质瘤患者组织中MGMT和hMLH1的启动子区甲基化状态;应用免疫组织化学方法检测其蛋白表达水平。结果 MGMT启动子区甲基化43例(55.1%),hMLH1启动子区甲基化32例(41.0%)。MGMT与hMLH1在胶质瘤中表达的阳性细胞百分比的中位数分别为15.9%和84.6%。两种基因的启动子区甲基化状态与蛋白表达的阳性率没有明显的相关性,且均与年龄、性别、病理类型无关。结论胶质瘤细胞中同属于DNA修复系统的MGMT蛋白表达率远低于hMLH1表达率,这提示胶质瘤发生发展过程中可能存在着与DNA修复系统紊乱有关的一些独特的路径。

关键词: 胶质瘤, MGMT, hMLH1, 免疫组织化学, 甲基化特异性PCR

Abstract: Objective To explore the methylation status and expression of hMLH1 and MGMT in glioma, and the role of them in the glioma oncogenesis. Methods Methylation status of the MGMT and hMLH1 promoter regions was assayed in 78 glioma tissues by methylation-specific PCR(MSP). The expression of MGMT and hMLH1 in the glioma was investigated by immunohistochemical technique using monoclonal antibody. Results Methylation in the MGMT and hMLH1 promoter regions was found in 43(55.1%) and 32(41.0%) cases respectively. The median of expression rates of MGMT and hMLH1 in tumor cells were 15.9% and 84.6% respectively. Methylation status in the promoter region showed no obvious correlation with the percentage of expression in tumor cells, and the sex, age, and pathological type. Conclusion As proteins of DNA repair system, the expression of MGMT is much lower than that of hMLH1, suggesting that a number of different pathways may exist in gliomas which is associated with disturbances of DNA repair system.

Key words: glioma, MGMT, hMLH1, immunohistochemistry, methylation-specific PCR

中图分类号:

R 739. 4

陈慧媛;江涛;袁芳;崔云;李桂林;黄磊. 胶质瘤中MGMT和hMLH1甲基化与表达水平的变化及意义[J]. 首都医科大学学报, 2009, 30(2): 203-207.

CHEN Hui-yuan;JIANG Tao;Yuan Fang;CUI Yun;LI Gui-lin;HUANG Lei. The Methylation Status and Expression of MGMT and hMLH1 in Glioma and Their Clinical Significance[J]. Journal of Capital Medical University, 2009, 30(2): 203-207.

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