胶质瘤患者抑癌基因RASSF1A启动子区甲基化研究

目的探讨RASSF1A抑癌基因在胶质瘤组织及脑正常组织中甲基化程度及与临床特征的关系。方法46例脑胶质瘤组织及6例脑正常组织采自手术患者。用甲基化特异性聚合酶链反应（MS—PCR）方法检测46例胶质瘤（其中包括星形细胞瘤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基因甲基化状态。并对RASSF1甲基化发生率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基因甲基化发生率为65．2％（30／46）；6例脑正常组织中RASSF1A基因启动子未发生甲基化；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，P〈0．05）。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，胶质母细胞瘤甲基化发生频率分别为63．2％（12／19），68．8％（11／16），63．6％（7／11）。在各组之间甲基化发生率比较均无统计学意义，（P〉0．05）。②RASSF1A基因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。

Research on promoter hypermethylation of RASSF1 A tumor suppressor gene in glioma

Objective To investigate the promoter hypermethylation status of suppressor gene RASSF1A in glioma and normal brain tissues and its clinical pathological significance. Methods The promoter methylation status of the promoter region of RASSF1A was analyzed by methylation specific-polymerase chain reaction （ MSPCR） in 46 case of surgical resected gliomas （including 19 cases of astrocytoma, 16 cases of apendymoma, 11 case of glioblastomas） and 6 cases of normal brain tissues. Results The promoter methylation rate of RASSF1A was 65.2% （30/46）in glioma and 0 （0/6） in normal brain tissues. The frequency of promoter hypermethylation rate of RASSF1A in glioma and normal brain tissues presented significant correlation （65.2% vs 0, P = 0.017, P 〈 0.05 ）. The frequency of promoter methylation rate of RASSF1A in astrocytoma, ependymoma and glioblastomas were 63.2% （12/19）, 68.8% （11/16）, and 63.6% （7/11）, respectively, with no significant difference among them （P 〉0.05 for all）. However, the promoter methylation of RASSF1A in gliomas was not statistically related to the clinical characteristics of patients （differentiation grade and the size of tumors）. Conclusion There is a significant frequency of promoter methylation of RASSF1A in glioma, but not in normal brain tissues. The promoter methylation of RASSF1A in glioma may be an important molecular change and may contribute to the cause and development of glioma.