The Methylation And The Mutation Of Glioma--Associated Gene

Objective: The current therapies for gliomas are inefficacious. As other cancers in human, the genesis and progress of gliomas involve oncogenes, tumor suppressor genes and DNA repair genes, which are changed in structure and expression. The promoter hypermethylation of DNA repair gene O6-metrhylguanine- DNA methyltransferase (MGMT) and the relationship between the promoter hypermethylation of MGMT to clinic features in gliomas were examined. We also assess the frequency of p57KIP2 gene mutation in gliomas.Methods: DNA obtained 67 cases of gliomas, 2 cases of glioma cell lines, 23 cases of menigiomas and 12 cases of brain tissues were subjected to MGMT promoter methylation study using MSP. All cases were confirmed by image and pathological diagnosis. We analysed the entire coding sequence of p57KIP2, including intrion-exon boundaries, by single strand conformation polymorphism(SSCP).Results: In gliomas, the aberrant promoter methylation of MGMT was detected in 40. 3%(27/67) of the tumors, whereas in meningiomas and normal brain tissues, this alteration was no found. This finding was associated with regression of the diameter of the gliomas and the ratio of the promoter methylation, no regression of age, gender, the position of the gliomas. There is no statistical difference among the grades of the glioma. Significant correlation between methylation status of medulloblastoma and the other gliomas was found. Analysis of p57KIP2 gene by SSCP revealed mutation in 3 cases of p57KIP2 exon 1 case and 1 of exon 2, but no statistical difference. No mutations were found in normal brain tissue and meningioma.Conclusions: Our results suggest that promoter methylation of MGMT plays an important role in glioma. p57KIP2 silencing may involve in other mechanisms in the pathogenesis of gliomas.