成人IDH野生型弥漫性胶质瘤的临床病理学及分子遗传学特征  

Clinicopathological and molecular genetic characteristics of adult IDH wild-type diffuse gliomas

作　　者：王雷明[1] 王玮[1] 刘莉 高敏 姚盈盈 张萌 熊艳蕾 邵阳 卢德宏[1] 滕梁红[1] Wang Leiming;Wang Wei;Liu Li;Gao Min;Yao Yingying;Zhang Meng;Xiong Yanlei;Shao Yang;Lu Dehong;Teng Lianghong(Department of Pathology,Xuanwu Hospital,Capital Medical University,Beijing 100053,China;Nanjing Geneseeq Technology Inc.,Nanjing 210000,China)

机构地区：[1]首都医科大学宣武医院病理科,北京100053 [2]南京世和基因生物技术股份有限公司,210000

出　　处：《中华病理学杂志》2021年第7期734-739,共6页Chinese Journal of Pathology

基　　金：北京市医院管理中心临床医学发展专项经费资助(ZYLX202113);北京市科技新星计划(Z201100006820149)。

摘　　要：目的探讨成人IDH野生型(isocitrate dehydrogenase wildtype)弥漫性胶质瘤的临床病理学和分子遗传学特征及其预后意义。方法收集2016—2020年首都医科大学宣武医院共87例成人IDH野生型弥漫性胶质瘤病例进行回顾性研究,分析其临床病理特征,并利用直接测序及二代测序检测其相关分子遗传学特征,同时分析与预后相关的影响因素。结果87例IDH野生型弥漫性胶质瘤中,男性53例,女性34例;年龄19~78岁(平均年龄53岁)。组织学诊断包括弥漫性星形细胞瘤6例(6.9%)、间变性星形细胞瘤16例(18.4%)、间变性少突星形细胞瘤1例(1.1%)、间变性少突胶质细胞瘤1例(1.1%)、胶质母细胞瘤63例(72.4%)。IDH野生型胶质瘤中TERT启动子突变60例(69.0%)、MGMT启动子甲基化43例(49.4%)、EGFR基因变异38例(43.7%)、PTEN基因变异35例(40.2%)及TP53突变32例(36.8%),是常见的分子遗传学改变;同时检测到17例(19.5%)存在PDGFRA变异,15例(17.2%)存在CDK4扩增及11例(12.6%)存在MDM2扩增等。IDH野生型弥漫性胶质瘤中,TERT启动子、EGFR、PTEN、TP53、PDGFRA、CDK4、MDM2等基因变异常同时共存,并与各基因野生型之间总生存期差异均无统计学意义(P>0.05);在WHOⅡ/Ⅲ级胶质瘤中存在上述基因变异者预后较差,与胶质母细胞瘤患者总生存期相似,差异无统计学意义(P>0.05)。结论TERT启动子、EGFR、PTEN、TP53、PDGFRA、CDK4及MDM2等基因变异是成人IDH野生型胶质瘤中常见的分子遗传学改变,IDH野生型WHOⅡ/Ⅲ级胶质瘤中存在上述基因变异提示预后不良。建议对IDH野生型胶质瘤行上述基因检测,以进一步整合诊断并为临床提供预后相关的分子遗传学因素。Objective To analyze the clinicopathological and molecular features and prognostic implications of adult isocitrate dehydrogenase wild type(IDH-wt)diffuse gliomas.Methods A total of 87 cases of adult IDH-wt diffuse gliomas from 2016 to 2020 in Xuanwu Hospital of Capital Medical University were retrospectively collected.The clinicopathological characteristics and prognosis were analyzed.Molecular characteristics were also analyzed using Sanger sequencing and next generation sequencing.Results There were 53 males and 34 females,aged from 19 to 78 years(mean 53 years).Histopathologically,there were 63(72.4%)glioblastomas,16(18.4%)anaplastic astrocytomas,six(6.9%)diffuse astrocytomas,and one(1.1%)each of anaplastic oligodendrocytoma,and anaplastic oligodendroglioma.Common molecular genetic changes in IDH-wt gliomas included TERT promoter mutation which was found in 60 cases(69.0%);MGMT promoter methylation in 43 cases(49.4%);EGFR mutation in 38 cases(43.7%);PTEN mutation in 35 cases(40.2%)and TP53 mutation in 32 cases(36.8%).In addition,PDGFRA mutation was detected in 17 cases(19.5%),CDK4 amplification in 15 cases(17.2%)and MDM2 amplification in 11 cases(12.6%).In IDH-wt diffuse gliomas,there was no significant difference in the overall survival between TERT promoter,EGFR,PTEN,TP53,PDGFRA,CDK4,MDM2 mutations and the wild-type,since these gene mutations could co-occur in any case(P>0.05).Also there was no significant difference in the overall survival between the WHO gradeⅡ/Ⅲgliomas and glioblastoma patients with these gene mutations(P>0.05).Conclusions TERT promoter,EGFR,PTEN,TP53,PDGFRA,CDK4 and MDM2 gene mutations are common molecular genetic changes in adult IDH-wt gliomas,and are associated with poor prognosis.It is suggested that these genes are potentially useful for predicting the prognosis and should be tested in adult IDH-wt gliomas.

关 键 词：神经胶质瘤 高通量核苷酸测序 成年人 DNA突变分析 

分 类 号：R739.41[医药卫生—肿瘤]