The revised 4th edition of the 2016 World Health Organization Classification of Tumors of the Central Nervous System (2016 CNS WHO) has introduced the integrated diagnostic classification that combines molecular and histological diagnoses for diffuse gliomas. In this study, we evaluated the molecular alterations for consecutive 300 diffuse glioma cases (grade 2, 56; grade 3, 62; grade 4, 182) based on this classification. Mutations in the isocitrate dehydrogenase (IDH) genes were common in lower grade glioma (LGG: grade2–3), and when combined with 1p/19q status, LGGs could be stratified into three groups except for four cases (Astrocytoma, IDH-mutant: 44; Oligodendroglioma, IDH-mutant and 1p/19q codeleted: 37; Astrocytoma, IDH-wildtype: 33). 1p/19q-codeleted oligodendrogliomas were clinically the most favorable subgroup even with upfront chemotherapy. In contrast, IDH-wildtype astrocytomas had a relatively worse prognosis; however, this subgroup was more heterogeneous. Of this subgroup, 11 cases had TERT promoter (pTERT) mutation with shorter overall survival than 12 pTERT-wildtype cases. Additionally, a longitudinal analysis indicated pTERT mutation as early molecular event for gliomagenesis. Therefore, pTERT mutation is critical for the diagnosis of molecular glioblastoma (WHO grade 4), regardless of histological findings, and future treatment strategy should be considered based on the precise molecular analysis.

世界卫生组织 2016 年修订的第 4 版中枢神经系统肿瘤分类 (2016 CNS WHO) 引入了综合诊断分类，将分子和组织学诊断相结合，对弥漫性神经胶质瘤进行了诊断。在本研究中，我们根据该分类评估了连续 300 例弥漫性胶质瘤病例（2 级，56 例；3 级，62 级；4 级，182 例）的分子改变。异柠檬酸脱氢酶 (IDH) 基因突变在低级别胶质瘤（LGG：2-3 级）中很常见，当结合 1p/19q 状态时，LGG 可以分为三组，除了 4 例（星形细胞瘤，IDH 突变： 44；少突胶质细胞瘤，IDH突变体和 1p/19q 编码：37；星形细胞瘤，IDH-野生型：33）。1p/19q-codeleted 少突胶质细胞瘤在临床上是最有利的亚组，即使进行了前期化疗。相比之下，IDH -wildtype星形细胞瘤者预后相对较差; 然而，这个亚组更加异质。在该亚组中，11 例具有TERT启动子 (p TERT ) 突变，其总生存期比 12 p TERT野生型病例短。此外，纵向分析表明 p TERT突变是胶质瘤发生的早期分子事件。因此，p TERT 无论组织学发现如何，突变对于分子胶质母细胞瘤（WHO 4级）的诊断至关重要，应根据精确的分子分析考虑未来的治疗策略。