摘要
目的应用全外显子测序技术探讨端粒酶反转录酶(TERT)启动子突变在脑胶质瘤分子分型诊断中的价值.方法回顾性纳入2016年3月至2018年10月于山东大学齐鲁医院神经外科行手术治疗且术后病理学检查确诊为脑胶质瘤的135例患者,利用全外显子测序技术检测其胶质瘤相关分子特征,分析TERT启动子突变与其他胶质瘤分子特征以及肿瘤病理学类型的关系,从而探讨TERT启动子突变在胶质瘤分子分型诊断中的价值.结果135例患者中,35例(25.9%)存在TERT启动子突变,且TERT启动子突变与染色体1p/19q联合缺失有关(x^(2)=14.190,P<0.001),而与异柠檬酸脱氢酶(IDH)基因突变无明显相关(x^(2)=0.827,P=0.363).在世界卫生组织(WHO)Ⅱ级和Ⅲ级IDH突变型星形细胞瘤以及WHOⅣ级IDH突变型胶质母细胞瘤组(简称星形-突变型组)中,TERT启动子的突变率低于WHOⅡ级和Ⅲ级的IDH突变伴染色体1p/19q联合缺失型少突胶质细胞瘤组(简称少突组)以及WHOⅣ级IDH野生型胶质母细胞瘤、IDH野生型巨细胞型胶质母细胞瘤和IDH野生型胶质肉瘤组(简称胶母-野生型组)(均P<0.001),而少突组与胶母-野生型组之间TERT启动子突变率的差异无统计学意义(P>0.05).WHOⅡ级和Ⅲ级星形细胞瘤患者中,无一例同时存在TERT启动子突变与IDH基因突变.结论TERT启动子突变主要存在于IDH突变伴染色体1p/19q联合缺失型少突胶质细胞瘤以及IDH野生型胶质母细胞瘤患者中.TERT启动子突变与IDH基因突变同时存在可能能够排除WHOⅡ、Ⅲ级星形细胞瘤的诊断.
Objective To explore the value of telomerase revese transcriptase(TERT)promoter mutations in the diagnosis of molecular typing in gliomas by using whole exome sequencing technology.Methods A retrospective study was conducted on 135 patients with gliomas who were surgically treated and pathologically confirned between March 2016 and October 2018 at Department of Neurosurgery,Qilu Hospital of Shandong University.Molecular characterization of gliomas was detected by whole exome sequencing.The relationship between TERT promoter mutations and other pathological characteristics was determined to explore the value of TERT promoter mutations in the diagnosis of molecular typing in gliomas.Results Among 135 patients with gliomas,TERT promoter mutations were detected in 35 cases(25.9%).TERT promoter mutations were associated with 1p/19q-codeletion(X^(2)=14.190,P<0.001)rather than IDH mutations(x^(2)=0.827,P=0.363).The frequency of TERT promoter mutations in the"astrocytoma-mut"group(including WHO grade Ⅱ,Ⅱ astroeytomas,IDH-mutant and WHO grade Ⅳ glioblastoma,IDH-mutant)was lower than that in the"oligodendroglioma"group(ineluding WHO grade Ⅱ,Ⅰ oligodendrogliomas,1IDH-mutant and 1p/19q-codeleted)as well as that in"glioblastoma-wt"group(including WHO IV glioblastoma,IDI-wildtype,giant cell glioblastoma,IDH-wildtype and gliosarcoma,IDH-wildtype)(both P<0.001).There was no signifieant difference in the frequency of TERT promoter mutations between the"goligodendrogliom"group and"glioblastoma-wt"group(P>0.05).TERT promoter mutation and IDH mutation were not present in WHO Ⅲ astrocytoma patients simultaneously.Conclusions The TERT promoter mutation is mainly present in oligodendroglioma,IDH-mutant and 1p/19q codeleted and glioblastoma,IDH-wildtype.The coexistence of TERT promoter mutation with IDH mutations may exclude the diagnosis of WHO Ⅱ or Ⅱ astroeytoma.
作者
王皓
薛皓
赵荣荣
邱伟
李复生
李明昕
梁承星
单德志
杨国正
李刚
Wang Hao;Xue Hao;Zhao Rongrong;Qiu Wei;Li Fusheng;Li Mingxin;Liang Chengxing;Shan Dezhi;Yang Guozheng;Li Gang(Department of Neurosurgeryt Qilu Hospital,Shandong University,Jinan 250012,China)
出处
《中华神经外科杂志》
CSCD
北大核心
2021年第4期400-405,共6页
Chinese Journal of Neurosurgery
基金
山东省自然科学基金(2017CXGC1203,2017G006012)
山东省泰山学者攀登计划专家(tspd20210322)
山东大学临床研究重点项目(2020SDUCRCA011)。
关键词
神经胶质瘤
诊断
分子分型
点突变
端粒酶反转录酶
Gliona
Diagnosis
Molecular typing
Point mutation
Telomerase reverse transeriptase
