Liu Q Q, Yin X X, Zou Y, Yu T P, Gong J, Chen X Q, Nie L, Xu M, Zhang M N, Zhou Q, Chen N
Department of Pathology, West China Hospital, Chengdu 610041, China.
Zhonghua Bing Li Xue Za Zhi. 2018 Sep 8;47(9):658-663. doi: 10.3760/cma.j.issn.0529-5807.2018.09.002.
To investigate the status and prognostic significance of TERT and IDH1/2 genes mutations in diffusely infiltrating gliomas. Hot spot mutations of TERT and IDH1/2 genes were detected by DNA sequencing in 236 cases of gliomas at West China Hospital from 2012 to 2016, including pilocytic astrocytoma (WHO grade Ⅰ, 16 cases), diffuse astrocytoma and oligodendroglioma (WHO grade Ⅱ, 89 cases), anaplastic astrocytoma and oligodendroglioma (WHO grade Ⅲ, 72 cases) and glioblastoma (WHO grade Ⅳ, 59 cases). The prognostic significance of TERT and IDH1/2 hot spot mutations was evaluated. No IDH or TERT mutations were detected in pilocytic gliomas. TERT promoter mutation frequency was higher in patients aged ≥40 years(60.8%, 93/153) than in patients aged <40 years (32.8%, 22/67; <0.01). TERT promoter mutation rate was also significantly higher in oligodendroglioma (87.5% , 56/64) than that in astrocytoma(37.8%, 59/156; <0.01). Young age (<40 years), oligodendroglioma and IDH1 mutation were favorable prognostic factors for diffusely infiltrating astrocytic and oligodendroglial tumors. TERT mutation alone was not of prognostic significance. Diffusely infiltrating astrocytic and oligodendroglial tumors were divided into four molecular subtypes according to TERT and IDH1 mutation status: IDH(+ )/TERT(+ ), IDH(+ )/TERT(-), IDH(-)/TERT(-) and IDH(-)/TERT(+ ). There was significant prognostic difference among the 4 subtypes. Combined IDH and TERT gene mutation analysis may be useful for prognostic subgrouping. Notably, IDH1 wild-type cases can be further subdivided into TERT(+ ) or (-) subgroups with significant prognostic difference.
探讨端粒酶逆转录酶（TERT）和异柠檬酸脱氢酶1/2（IDH1/2）基因在弥漫性浸润性胶质瘤中的突变情况及其预后意义。2012年至2016年，采用DNA测序法检测了四川大学华西医院236例胶质瘤患者TERT和IDH1/2基因的热点突变，其中包括毛细胞型星形细胞瘤（WHO Ⅰ级，16例）、弥漫性星形细胞瘤和少突胶质细胞瘤（WHO Ⅱ级，89例）、间变性星形细胞瘤和少突胶质细胞瘤（WHO Ⅲ级，72例）以及胶质母细胞瘤（WHO Ⅳ级，59例）。评估TERT和IDH1/2热点突变的预后意义。毛细胞型胶质瘤未检测到IDH或TERT突变。年龄≥40岁患者的TERT启动子突变频率（60.8%，93/153）高于年龄<40岁患者（32.8%，22/67；P<0.01）。少突胶质细胞瘤的TERT启动子突变率（87.5%，56/64）也显著高于星形细胞瘤（37.8%，59/156；P<0.01）。年轻（<40岁）、少突胶质细胞瘤和IDH1突变是弥漫性浸润性星形细胞和少突胶质细胞肿瘤的有利预后因素。单独的TERT突变无预后意义。根据TERT和IDH1突变状态，将弥漫性浸润性星形细胞和少突胶质细胞肿瘤分为四种分子亚型：IDH(+)/TERT(+)、IDH(+)/TERT(-)、IDH(-)/TERT(-)和IDH(-)/TERT(+)。这四种亚型的预后存在显著差异。联合IDH和TERT基因突变分析可能有助于预后亚组划分。值得注意的是，IDH1野生型病例可进一步分为TERT(+)或(-)亚组，其预后差异显著。
