TERT mutation in glioma: Frequency, prognosis and risk

• TERT mutations occurred frequently in GBM and oligodendrogliomas.
• TERT promoter 292 mutations confer a poor prognosis on glioma patients.
• TERT polymorphisms were associated with an increased risk of glioma.

Telomerase reverse transcriptase (TERT) has received a great deal of attention in recent years for its role as a prognostic and predictive molecular marker of glioma. However, the results of studies examining its mutation frequency and predictive value are inconsistent, and several studies have investigated the association between TERT gene polymorphisms and gliomagenesis. We used a meta-analysis approach to examine these unsolved problems. A bibliography search using EMBASE and MEDLINE was performed to identify potentially relevant articles and conference abstracts that investigated TERT mutations in glioma. The references contained in the identified trials were also examined to identify any other relevant published or unpublished articles. Sixteen studies were included. Pooled estimates of the relative risks (RR), 95% confidence intervals (95% CI), hazard ratios (HR) and frequency were calculated. TERT mutations occurred frequently in glioblastoma (69%) and oligodendrogliomas (72%) but were less frequent in astrocytomas (24%) and oligoastrocytomas (38%). The HR for glioma patients with TERT mutations versus wild type TERT was 1.63 (95% CI 1.35–1.98). TERT polymorphisms were associated with an increased risk of glioma compared to controls (RR = 1.28, 95% CI 1.23–1.33). Our study shows that the TERT gene is a valuable prognostic and predictive biomarker of glioma, and TERT gene polymorphisms are significantly associated with an increased risk of glioma.