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

Area of Science:

• Neuro-oncology
• Molecular diagnostics
• Cancer genomics

Background:

• The 2021 WHO Classification of CNS Tumors emphasizes molecular markers, including TERT promoter (TERTp) mutations, for glioma reclassification.
• TERTp mutations are critical for diagnosing glioblastoma and understanding glioma heterogeneity.

Purpose of the Study:

• To investigate the distribution and prognostic significance of TERT promoter mutations in gliomas based on the latest WHO classification.
• To explore correlations between TERTp mutations and other molecular alterations across different glioma subgroups.

Main Methods:

• Analysis of TERT promoter mutations and 59 other gene alterations/chromosome copy number variations in 207 glioma patients.
• Patient samples were collected from Peking Union Medical College Hospital between 2011 and 2022.

Main Results:

• TERTp mutations occurred in 4.55% of astrocytomas, 100% of oligodendrogliomas, and 77.92% of glioblastomas.
• TERTp mutation predicted better prognosis in IDH-mutant grade 2 gliomas but was associated with poorer outcomes in Grade 4 gliomas and IDH-wildtype grade 2/3 gliomas.
• TERTp mutations showed specific co-occurrence patterns with other molecular markers (e.g., EGFR, CIC, ATRX) in different glioma subtypes.

Conclusions:

• TERTp mutation status is a significant factor influencing glioma prognosis across various subtypes.
• Understanding TERTp mutation distribution and its molecular correlations can refine prognostic predictions and aid in glioma classification.