TERTp Mutation and its Prognostic Value in Glioma Patients Under the 2021 WHO Classification: A Real-World Study

Hao Xing; Delin Liu; Junlin Li; Yulu Ge; Xiaopeng Guo; Wenlin Chen; Dachun Zhao; Yixin Shi; Yilin Li; Yaning Wang; Yuekun Wang; Yu Xia; Jiaming Wu; Tingyu Liang; Hai Wang; Qianshu Liu; Shanmu Jin; Tian Qu; Siying Guo; Huanzhang Li; Tianrui Yang; Kun Zhang; Yu Wang; Wenbin Ma

doi:10.1002/cam4.70533

TERTp Mutation and its Prognostic Value in Glioma Patients Under the 2021 WHO Classification: A Real-World Study

Cancer Med. 2025 Jan;14(2):e70533. doi: 10.1002/cam4.70533.

Authors

Hao Xing¹, Delin Liu^{1

2}, Junlin Li^{1

2}, Yulu Ge^{1

2}, Xiaopeng Guo^{1

3}, Wenlin Chen¹, Dachun Zhao⁴, Yixin Shi^{1

2}, Yilin Li^{1

2}, Yaning Wang¹, Yuekun Wang¹, Yu Xia^{1

2}, Jiaming Wu^{1

2}, Tingyu Liang¹, Hai Wang¹, Qianshu Liu^{1

2}, Shanmu Jin^{1

2}, Tian Qu^{1

2}, Siying Guo^{1

2}, Huanzhang Li^{1

2}, Tianrui Yang^{1

2}, Kun Zhang^{1

2}, Yu Wang^{1

3}, Wenbin Ma^{1

3}

Affiliations

¹ 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.
² Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
³ China Anti-Cancer Association Specialty Committee of Glioma, Beijing, China.
⁴ Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Abstract

Background: 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.

Aims: 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.

Methods: 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.

Results: 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.

Keywords: TERT promoter mutation; adult‐type diffuse glioma; glioma classification; molecular subgroups; prognosis.

Abstract

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