中文摘要：

目的分析星形细胞胶质瘤患者IDH1基因突变分布与病理级别、预后的关系；探讨DNA甲基化是否为IDH1基因调控的模式之一。方法直接测序法检测91例星形细胞胶质瘤组织样本中IDH1的突变分布；重亚硫酸盐测序法检测9例星形细胞胶质瘤中IDH1启动子DNA甲基化水平。结果91例星形细胞胶质瘤患者中35例存在IDH1突变（38．5％），均为R132H突变。WHOI级肿瘤中未检测到IDH1突变；WHOⅡ-Ⅳ级原发性星形细胞胶质瘤中IDH1突变率分别为70．6％、62．1％、12．5％，突变率与病理级别呈负相关（r=0．522，P〈0．001）；7例继发性多形性胶质母细胞瘤中有5例（71．4％）发生突变，突变类型与原发肿瘤一致。IDH1突变型胶质瘤患者中位生存期较IDH1野生型患者明显延长（P〈0．05）。9例胶质瘤患者IDH1启动子均未检测到DNA甲基化改变。结论IDH1突变在星形细胞胶质瘤中发生频繁，是预后改善的指标；DNA甲基化可能未参与IDH1基因表达的调控。

英文摘要：

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 IDH1 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 1I astrocytoma, 62. 1% in primary WHO grade 11I 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.