脑膜瘤MLH1启动子甲基化水平及临床意义

Level of MLH1 pomoter methylation and its clinical meanings in meningiomas

目的探讨脑膜瘤mut L同源基因1（MLH1）启动子甲基化水平与脑膜瘤侵袭性的相关性。方法从我院标本库随机选取64例脑膜瘤石蜡包埋组织标本,其中侵袭性脑膜瘤26例,非侵袭性脑膜瘤38例。应用逆转录-PCR检测MLH1 m RNA表达水平,应用特异高分辨率熔解（MS-HRM）曲线检测不同侵袭性脑膜瘤MLH1启动子甲基化水平。结果侵袭性脑膜瘤MLH1m RNA含量比非侵袭性脑膜瘤显著降低（P〈0.05）。MS-HRM曲线分析显示,侵袭性脑膜瘤MLH1启动子区高度甲基化水平为0-1%所占比例（7.7%,2/26）显著低于非侵袭性脑膜瘤（55.3%,21/38;P〈0.05）。结论 MLH1启动子区甲基化可能下调MLH1的表达,进而调控脑膜瘤侵袭性行为。

Objective To establish a method to determine mut L momolog1（MLH1） promoter methylation level in themeningiomas and analyze the relationship between MLH1 methylation level and meningioma invasiveness.MethodsDNA was extractedfrom 64 samples of the meningiomas, of which, 26 were invasive meningiomas and 38 non-invasive ones, and the methylationmodification of DNA was performed according to instruction book. The standard methylation MLH1 DNA was diluted bynon-methylation MLH1 DNA in different proportion of 100%, 50%, 25%, 12.5% and 1% to establish the standard methylation sensitivehigh resolution melting curve. MLH1 promoter methylation level was determined quantitatively by the method of MS-HRM method in allthe invasive meningiomas and non invasive meningiomas. The relationship of MLH1 promoter methylation level with meningiomainvasiveness was analyzed.ResultMLH1 promoter methylation level was significantly higher in the invasive meningiomas than that inthe non invasive meningiomas（P〈0.01）.ConclusionThe present result suggests that MLH1 promoter methylation level may play animportant role in the pathogenesis of the invasiveness of the meningiomas.