Analysis of the role of hMLH1 hypermethylation and microsatellite instability in meningioma progression.

ABSTRACT

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.