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

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。

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

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.