Xing Hao, Liu Delin, Li Junlin, Ge Yulu, Guo Xiaopeng, Chen Wenlin, Zhao Dachun, Shi Yixin, Li Yilin, Wang Yaning, Wang Yuekun, Xia Yu, Wu Jiaming, Liang Tingyu, Wang Hai, Liu Qianshu, Jin Shanmu, Qu Tian, Guo Siying, Li Huanzhang, Yang Tianrui, Zhang Kun, Wang Yu, Ma Wenbin
Department of Neurosurgery, Center for Malignant Brain Tumors, National Glioma MDT Alliance, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Cancer Med. 2025 Jan;14(2):e70533. doi: 10.1002/cam4.70533.
The 2021 WHO Classification of Central Nervous System Tumors introduces more molecular markers for glioma reclassification, including TERT promoter (TERTp) mutation as a key feature in glioblastoma diagnosis.
Given the changes in the entities included in each subtype under the new classification, this research investigated the distribution, prognostic value, and correlations with other molecular alterations of TERTp mutation in different subgroups under this latest classification.
All glioma patients admitted to Peking Union Medical College Hospital for surgical resection or biopsy from 2011 to 2022 were included. Samples were analyzed for TERTp mutation and 59 other gene alterations and chromosome copy number variations.
A total of 207 patients were included. The occurrence of TERTp mutations varied with percentages of 4.55%, 100%, and 77.92% in astrocytoma, oligodendroglioma, and glioblastoma, respectively. 65% of all adult-type glioma patients and 42.6% of IDH-wildtype histology grade 2 or 3 patients were TERTp-mutant. Survival analysis showed that TERTp mutation was a predictor of better prognosis in IDH-mutant grade 2 gliomas (median OS (mOS): not reached (NA) (95% CI: NA-NA) vs. 75.9 (95% CI: 55.4-NA) months, HR = 0.077 (95% CI: 0.01-0.64), p = 0.003), while poor OS was associated with all Grade 4 gliomas (mOS: 17.5 (95% CI: 12.6-24.2) vs. 40.5 (95% CI: 24.4-83.8) months, HR = 2.014 (95% CI: 1.17-3.47), p = 0.01) and all IDH-wildtype histology grade 2 or 3 gliomas (median OS: 12.6 (95% CI: 11-24.2) vs. 83.8 (95% CI: 35.2-NA) months, HR = 3.768 (95% CI: 1.83-7.78), p < 0.001). Moreover, TERTp mutation tended to co-occur with EGFR, KRAS, and MET in glioblastoma. In the IDH-mutant subgroup, it tended to co-occur with CIC and FUBP1 alterations, while being mutually exclusive with ATRX and TP53 alterations. These correlations may further refine prognostic predictions.
2021年世界卫生组织中枢神经系统肿瘤分类引入了更多用于胶质瘤重新分类的分子标志物，包括端粒酶逆转录酶启动子（TERTp）突变作为胶质母细胞瘤诊断的关键特征。
鉴于新分类下各亚型所包含实体的变化，本研究调查了TERTp突变在这一最新分类下不同亚组中的分布、预后价值以及与其他分子改变的相关性。
纳入2011年至2022年在北京协和医院接受手术切除或活检的所有胶质瘤患者。对样本进行TERTp突变以及59种其他基因改变和染色体拷贝数变异分析。
共纳入207例患者。TERTp突变的发生率在星形细胞瘤、少突胶质细胞瘤和胶质母细胞瘤中分别为4.55%、100%和77.92%。所有成人型胶质瘤患者中有65%以及异柠檬酸脱氢酶（IDH）野生型组织学2级或3级患者中有42.6%为TERTp突变型。生存分析显示，TERTp突变是IDH突变型2级胶质瘤预后较好的预测指标（中位总生存期（mOS）：未达到（NA）（95%置信区间：NA - NA）与75.9（95%置信区间：55.4 - NA）个月，风险比（HR）= 0.077（95%置信区间：0.01 - 0.64），p = 0.003），而所有4级胶质瘤（mOS：17.5（95%置信区间：12.6 - 24.2）与40.5（95%置信区间：24.4 - 83.8）个月，HR = 2.014（95%置信区间：1.17 - 3.47），p = 0.01）以及所有IDH野生型组织学2级或3级胶质瘤（中位总生存期：12.6（95%置信区间：11 - 24.2）与83.8（95%置信区间：35.2 - NA）个月，HR = 3.768（95%置信区间：1.83 - 7.78），p < 0.001）的总生存期较差与之相关。此外，TERTp突变在胶质母细胞瘤中倾向于与表皮生长因子受体（EGFR）、 Kirsten大鼠肉瘤病毒癌基因（KRAS）和间质表皮转化因子（MET）共同发生。在IDH突变亚组中，它倾向于与CIC和FUBP1改变共同发生，而与α地中海贫血/智力发育迟缓综合征X连锁基因（ATRX）和肿瘤蛋白p53（TP53）改变相互排斥。这些相关性可能进一步优化预后预测。
