Benefit of MGMT methylation in glioblastoma in relation to hTERT promoter mutation.

2006Background: Human telomerase reverse transcriptase (hTERT) promoter mutation occurs in 70-80% of glioblastoma (GBM) and has been shown to enhance telomerase expression. No consensus has been established on the clinical significance of hTERT mutation in GBM. Methods: We retrospectively identified 303 IDH1 wildtype primary GBM patients treated with standard upfront chemo-radiotherapy and determined hTERT promoter genotype. 190 GBM patients from TCGA that also received standard treatment were used for validation, using hTERT expression as a surrogate for mutation. The primary objective was to assess the effect of hTERT status on overall survival (OS) and progression free survival (PFS) using Kaplan-Meier and Cox regression analyses. Results: hTERT promoter mutation was detected in 228 (75%) cases, in which 177 (78%) were C228T and 51 (22%) were C250T. hTERT mutant patients showed similar OS and PFS to hTERT wildtype patients. However, Cox analysis showed a strong interaction between hTERT promoter mutati...