摘要目的 探讨弥漫浸润性胶质肿瘤中端粒酶逆转录酶(TERT)及异柠檬酸脱氢酶(IDH)基因热点突变情况及二者结合的预后价值.方法 采用Sanger测序法检测四川大学华西医院2012至2014年手术的236例胶质瘤标本(WHOⅠ～Ⅳ级肿瘤分别为16、89、72和59例)中TERT基因启动子区(228位点和250位点)、IDH1(132密码子)和IDH2(172密码子)突变情况,分析这些突变与患者预后的关系.结果 WHOⅠ级16例毛细胞型星形细胞瘤中均未检出IDH和TERT基因突变.WHOⅡ～Ⅳ级的220例弥漫浸润性胶质肿瘤中,年龄≥40岁患者TERT突变比例(60.8％,93/153)明显高于<40岁患者(32.8％,22/67;P<0.01),少突胶质瘤中TERT突变率(87.5％,56/64)明显高于星形细胞瘤(37.8％,59/156;P<0.01).年龄<40岁、IDH1突变和少突胶质瘤为弥漫浸润性胶质肿瘤预后好的因素.TERT突变不能单独提示胶质瘤预后.TERT和IDH1突变联合检测可将弥漫浸润性胶质瘤分为4个分子亚组:IDH(+)/TERT(+)组、IDH(+)/TERT(-)组、IDH(-)/TERT(-)组和IDH(-)/TERT(+)组,4组间具有明显预后差异,IDH(+)/TERT(+)组患者预后最好,IDH(-)/TERT(+)组患者预后最差.结论 IDH和TERT基因突变状态可细化胶质瘤患者预后分组,特别是可将IDH1野生型的病例进一步进行预后亚组划分,具有较好的临床应用价值.

abstractsObjective To investigate the status and prognostic significance of TERT and IDH1/2 genes mutations in diffusely infiltrating gliomas. Methods 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. Results 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;P<0. 01 ) . TERT promoter mutation rate was also significantly higher in oligodendroglioma ( 87. 5％ , 56/64 ) than that in astrocytoma ( 37. 8％, 59/156;P<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. Conclusions 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.