胶质瘤中端粒酶逆转录酶启动子区突变分析及其预后意义  

TERT promoter mutation is a potential biomarker for predicting poor outcome in gliomas

作　　者：何洁[1,2] 万经海[2] 李学记[2] 钱海鹏[2] 孟肖利[2] 郝佳洁[3] 徐昕[3] 王明荣[3] 

机构地区：[1]安徽医科大学第二附属医院神经外科,安徽合肥230601 [2]中国医学科学院肿瘤医院神经外科,北京100021 [3]中国医学科学院北京协和医学院肿瘤医院分子肿瘤学国家重点实验室,北京100021

出　　处：《癌变．畸变．突变》2015年第5期361-365,共5页Carcinogenesis,Teratogenesis & Mutagenesis

基　　金：国家自然科学基金项目(81470112)

摘　　要：目的：探讨端粒酶逆转录酶（TERT）启动子区突变与胶质瘤患者临床病理指标的关系及其对预后的影响。方法：应用Sanger测序技术检测78例脑胶质瘤组织中TERT启动子区C228T和C250T位点的突变情况,分析TERT启动子区突变与临床病理指标的关系及其对预后的影响。结果：TERT启动子区突变在脑胶质瘤中的发生率为32.1%,在低级别（Ⅰ~Ⅱ）和高级别（Ⅲ~Ⅳ）胶质瘤中突变分别占28.0%和34.0%。其中少突星形细胞瘤中突变占57.1%,胶质母细胞瘤中突变占44.4%,低级别星形细胞瘤和少突胶质细胞瘤中突变分别占28.6%和23.1%。TERT启动子区突变与胶质瘤患者术后生存时间显著相关,突变型术后生存时间显著短于野生型（P=0.001）。按低级别和高级别分组独立分析后发现,TERT启动子区突变在低级别组和高级别组中均与不良预后相关（P值分别为0.019和0.018）。Cox回归分析表明,TERT启动子区突变和术后放化疗是独立的预后影响因素（P=0.002,HR=3.486,95%CI：1.591~7.637;P=0.004,HR=0.331,95%CI：0.156~0.699）。结论：TERT启动子区突变频繁发生于脑胶质瘤中,突变型胶质瘤患者预后不良。OBJECTIVE： To explore the correlation between TERT promoter mutations and clinicopathological features in patients with gliomas. METHODS： TERT promoter mutations were screened by direct DNA sequencing in a population-based collection of 78 glioma tissues. The correlation of TERT promoter mutations and the prognosis was analyzed. RESULTS： We identified TERT promoter mutations in 32.1% gliomas, including 28.0% in low grade tumors and 34.0% in high grade tumors. The mutations were much more common in oligoastrocytomas （57.1%） and glioblastomas （44.4%）, while much less prevalent in astrocytomas （28.6%） and oligodendrogliomas（23.1%）. Median overall survival of the patients harboring mutations in TERT promoter was longer than that without the mutations （P=0.001） in both low （P=0.019） and high grade gliomas （P=0.018）. Multivariate analysis revealed TERT promoter mutations and no postoperative adjuvant therapy as significant prognostic factors for shorter survival （P=0.002, HR=3.486, 95%CI： 1.591- 7.637; P=0.004, HR=0.331, 95%CI： 0.156-0.699）. CONCLUSION： TERT promoter mutations frequently occurred in gliomas, which was a prognostic factor of poor outcome for the patients with the same pathological grade gliomas.

关 键 词：神经胶质瘤 端粒酶逆转录酶 启动子区突变 预后 

分 类 号：R739.41[医药卫生—肿瘤]