Paradoxical prognostic impact of TERT promoter mutations in gliomas depends on different histological and genetic backgrounds

Aims: The purpose of this study was to explore the clinical significance of telomerase reverse transcriptase (TERT) promoter mutations in gliomas. Methods and results: We used DNA sequencing data to analyze 887 gliomas for TERT promoter mutations based on histological and genetic backgrounds. TERT promoter mutations were detected in 39.6% of low-grade gliomas, 40.3% of anaplastic gliomas, 44.7% of primary glioblastomas, 29.4% of secondary glioblastomas, and in 29.7% of Proneural, 38.6% of Neural, 41.8% of Classical, and 41.6% of Mesenchymal subtypes. Frequency of C250T mutation in recurrent gliomas was approximately half that in newly diagnosed gliomas. TERT exhibited improved prognosis when co-occurred with isocitrate dehydrogenase 1 (IDH1) and 1p19q alteration, but experienced inverse survival in the Mesenchymal subtype or tumor protein p53 (TP53) and epidermal growth factor receptor (EGFR) alteration. Furthermore, the five subtypes were classified based on the prognostic impact of the TERT mutation with different genetic backgrounds of glioma. Conclusion: We describe the TERT promoter mutation spectrum according to the histological, genetic, and molecular subtypes of glioma, which may aid in glioma subtype classification and have clinical implications.