Chen M N, Wang P, Zhang J, Zhou B Y, Mao Q, Liu Y H
The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Genet Mol Res. 2012 Nov 12;11(4):3933-41. doi: 10.4238/2012.August.17.7.
We investigated a possible role of hMLH1 hypermethylation and microsatellite instability in meningioma progression. Fifty meningomas were examined for methylation of hMLH1 using a methylation-specific PCR; 43 of them were analyzed for microsatellite instability using nine microsatellite markers. Loss of heterozygosity on chromosome 22q was detected using two markers. Two atypical meningiomas showed microsatellite instability at four loci; one was methylated on hMLH1 and the other was unmethylated. Nine meningiomas were found to have methylated hMLH1; the frequencies in the different grades of meningioma were one of 20, two of 16, and six of 14, respectively. We concluded that the methylation status of hMLH1 is associated with the meningioma grade but not with microsatellite instability. Loss of heterozygosity was detected in 22 cases in at least one marker. The frequency of loss of heterozygosity increased with meningioma grade, but the tendency was not significant. The correlation between loss of heterozygosity and methylation of the hMLH1 gene was also not significant. We conclude that hypermethylation of the promoter of hMLH1 is an epigenetic change in meningiomas and is associated with the tumor grade, while microsatellite instability is an uncommon event in meningiomas.
我们研究了hMLH1基因高甲基化和微卫星不稳定性在脑膜瘤进展中的可能作用。采用甲基化特异性PCR对50例脑膜瘤进行hMLH1甲基化检测；其中43例使用9个微卫星标记分析微卫星不稳定性。使用两个标记检测22号染色体长臂的杂合性缺失。2例非典型脑膜瘤在4个位点表现出微卫星不稳定性；其中1例hMLH1甲基化，另1例未甲基化。发现9例脑膜瘤hMLH1甲基化；在不同分级的脑膜瘤中，其频率分别为20例中的1例、16例中的2例和14例中的6例。我们得出结论，hMLH1的甲基化状态与脑膜瘤分级相关，但与微卫星不稳定性无关。在22例中至少有1个标记检测到杂合性缺失。杂合性缺失的频率随脑膜瘤分级增加，但趋势不显著。hMLH1基因杂合性缺失与甲基化之间的相关性也不显著。我们得出结论，hMLH1启动子的高甲基化是脑膜瘤中的一种表观遗传变化，与肿瘤分级相关，而微卫星不稳定性在脑膜瘤中是一种罕见事件。
