RASSF1A基因在胶质瘤组织中甲基化研究及临床意义

目的：探讨胶质瘤组织及脑正常组织中抑癌基因RASSF1A启动子区甲基化程度及与临床特征的关系。方法：采用甲基化特异性聚合酶链反应（MS-PCR）方法检测46例脑胶质瘤（其中星形细胞瘤19例，室管膜瘤16例，胶质母细胞瘤11例）及6例脑正常组织中RASSF1A基因启动子区甲基化状态。并对RASSF1A基因启动子区甲基化发生情况与临床各因素之间的关系进行分析。结果：（1）46例脑胶质瘤组织DNA标本中RASSF1A基因启动子区甲基化发生率为65．2％（30／46）；6例脑正常组织中RASSF1A基因未发生甲基化；RASSF1A在胶质瘤和脑正常组织之间发生甲基化率比较差异有显著性（P=0.017）。在46例脑胶质瘤中RASSF1A有30例发生甲基化，其中低级别组14例（14／26），高级别组16例（16／20），两组之间甲基化率比较无明显差异（P〉0．05）。其中星形细胞瘤、室管膜瘤、胶质母细胞瘤中甲基化发生率分别为63．2％（12／19）、68、8％（11／16）、63．6％（7／11），各组之间甲基化发生率比较均无统计学意义（P=0．211）。（2）RASSFIA基因启动子区甲基化程度与脑胶质瘤病理分型、肿瘤大小之间无显著相关性。结论：RASSF1A在胶质瘤中有甲基化发生，在脑正常组织中未发生甲基化，检测胶质瘤中RASSF1A基因启动子区甲基化情况对临床判断肿瘤发生发展有指导意义。

The clinical research on promoter methylation of the RASSF1A in glioma

Objective:To investigate the promoter hypermethylation status of tumor suppressor gene RASSF1A in gliomas and normal brain tissues and the clinical pathological significance.Methods:The promoter methylation status of the promoter region of RASSF1A was analyzed by methylation specific-PCR(MS-PCR) in 46 cases surgically resected gliomas(19 cases with astrocytoma,16 cases with ependymoma,11 cases with glioblastomas) and 6 cases normal brain tissues.Results:The promoter methylation rate of RASSF1A in glioma was 65.2%(30/46)and in normal brain tissues was 0(0/6).The rate of promoter hypermethylation of RASSF1A in glioma and normal brain tissues showed significant correlation(65.2% vs.0,P=0.017).while the promoter methylation rate of RASSF1A in astrocytoma,ependymoma and glioblastomas were 63.2%(12/19),68.8%(11/16),63.6%(7/11),respectively.No significant statistical difference was observed(P=0.211).However,the promoter methylation of RASSF1A in glioma were not statistically correlated with the clinical characteristics of patients with differentiation grade and the size of tumors.Conclusion:There is a significant frequency promoter methylation of RASSF1A in glioma and there is no promoter methylation of RASSF1A in normal brain tissues.The promoter methylation of RASSF1A in glioma may be an important molecular change and may contribute to the cause and developement in glioma.