脑胶质瘤组织中p16基因启动子区CpG岛甲基化检测及其临床意义研究  

Detection of promoter hypermethylation of p16 gene and analysis of its clinicopathological significance in human gliomas

作　　者：侯道荣[1] 马骏[2] 夏龙[1] 徐旭广[1] 张小平[1] 戴有金[1] 温泽锋[1] 郑媛[1] 

机构地区：[1]南京医科大学实验动物中心,江苏南京210029 [2]南京医科大学附属第二医院神经外科,江苏南京210029

出　　处：《现代生物医学进展》2009年第20期3890-3893,3889,共5页Progress in Modern Biomedicine

摘　　要：目的:研究脑胶质瘤中p16基因启动子区甲基化情况及其临床意义。方法:用甲基化特异性PCR技术检测42例脑胶质瘤组织和癌旁正常脑组织中p16基因启动子甲基化,并分析该基因启动子甲基化与临床病理特征之间的关系。结果:脑胶质瘤组织中p16基因异常甲基化率(38.27%)显著高于癌旁正常脑组织中p16基因的异常甲基化率(8.8%,P=0.000)。发生甲基化的肿瘤组织或者正常脑组织中p16基因mRNA和蛋白表达显著降低。此外,p16基因异常甲基化和肿瘤病理分级有相关性(P=0.007),而与患者性别、年龄及肿瘤类型等临床特征无关(P=0.669,0.869和0.944)。结论:p16基因启动子区CpG岛高甲基化与p16表达下调相关,推测p16启动子区CpG岛高甲基化是导致p16基因在脑胶质瘤中表达下调的重要因素,有望成为脑胶质瘤早期辅助诊断的分子标志物之一。Objective： To detect the aberrant promoter hypermethylation of p16 gene in human gliomas and analyze its clinicopathological significance. Methods： A methylation-specific PCR was performed for the detection of promoter hypermethylation of pl6 gene in 42 glioma tissue samples and 42 corresponding normal brain tissue samples. The correlation between the aberrant methylation of p l 6 gene and the clinicopathological factors was analyzed. Restdts： The promoter hypermethylation ratio of p16 gene in glioma tissues （38.27%） was significantly higher than that in corresponding normal brain tissues （8.8%, P=0.000）. The expression levels of p16 mRNA and protein in glioma or normal brain tissues with methylation weresignificantly lower than those with unmethylation. Moreover, we also found that the aberrant promoter methylation ofpl6 gene was significantly correlated with tumor stage （P=0.007）, but not correlated with sex, age and tumor types of patients （P=0.669, 0.869 and 0.944, respectively）. Conclusion： The hypermethylation of p16 gene in CpG island is associated with downregnlated p16 expression, and detection of the aberrant methylation ofpl6 gene promoter in human gliomas would offer an effective method for the earlier auxiliary diagnosis of this malignancy.

关 键 词：脑胶质瘤 P16基因 DNA甲基化 启动子 

分 类 号：R733[医药卫生—肿瘤]