OBJECTIVE: This study explored the effects of telomerase reverse transcriptase 
(TERT) promoter mutations on transcriptional activity of the TERT gene under 
hypoxic and temozolomide (TMZ) treatment conditions, and investigated the status 
and prognostic value of these mutations in gliomas.
METHODS: The effect of TERT promoter mutations on the transcriptional activity 
of the TERT gene under hypoxic and TMZ treatment conditions was investigated in 
glioma cells using the luciferase assay. TERT promoter mutations were detected 
in 101 glioma samples (grades I-IV) and 49 other brain tumors by sequencing. 
TERT mRNA expression in gliomas was examined by real-time PCR. Hazard ratios 
from survival analysis of glioma patients were determined relative to the 
presence of TERT promoter mutations.
RESULTS: Mutations in the TERT promoter enhanced gene transcription even under 
hypoxic and TMZ treatment conditions, inducing upregulation of TERT mRNA 
expression. Mutations were detected in gliomas, but not in meningiomas, 
pituitary adenomas, cavernomas, intracranial metastases, normal brain tissues, 
or peripheral blood of glioma patients. Patients with TERT promoter mutations 
had lower survival rates, even after adjusting for other known or potential risk 
factors, and the incidence of mutation was correlated with patient age.
CONCLUSION: TERT promoter mutations were specific to gliomas. TERT promoter 
mutations maintained its ability of inducing high transcriptional activity even 
under hypoxic and TMZ treatment conditions, and the presence of mutations was 
associated with poor prognosis in glioma patients. These findings demonstrate 
that TERT promoter mutations are novel prognostic markers for gliomas that can 
inform prospective therapeutic strategies.