IDH1 mutation and DNA methylation of astrocytic glioma patients

Abstract

Objective To investigate the relationship between isocitrate dehydrogenase 1 (IDH1)gene mutation and the pathological grade and prognosis in astrocytic glioma patients.And to identify whether DNA methylation is one of the IDH1 gene regulatory patterns.Methods IDH1 mutation was detected by direct sequencing in 91 astrocytic glioma tissue samples; DNA methylation of ID-H1 promoter was detected by bisulfite sequencing in 9 astrocytic glioma cases.Results IDH1 mutations were demonstrated in 35 of 91 cases (38.5％) and all mutations were the type of R132H.No mutation of IDH1 was detected in WHO grade Ⅰ astrocytoma.Frequent mutations of IDH1 were observed as 70.6％ in primary WHO grade Ⅱ astrocytoma,62.1％ in primary WHO grade Ⅲ astrocytoma,12.5％ in primary glioblastoma multiforme.Frequencies of IDH1 mutations were negatively correlated with WHO pathological grade Ⅱ ～ Ⅳ of primary astrocytic glioma (r =0.522,P ＜0.001).IDH1 mutations were found in 5 of 7 secondary glioblastomas (71.4％),and the type of mutation was consistent with that in primary tumors.The mutation of the IDH1 was significantly associated with better outcome in the patients of astrocytic gliomas (P ＜ 0.05).DNA methylation of IDH1 promoter was not found in 9 glioma patients.Conclusions IDH1 mutation occured frequently in astrocytic gliomas and is a favorable prognostic indicator.DNA methylation might not be involved in the regulation of IDH1 gene expression. Key words: Glioma; IDH1 ; Mutation; DNA methylation