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

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.

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.

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.