Preclinical and clinical implications of TERT promoter mutation in glioblastoma multiforme.

ABSTRACT: The promoter region of the telomerase reverse transcriptase gene (TERT) is mutated in a subpopulation of patients with glioblastoma multiforme (GBM). In the present study, preclinical and clinical implications of the mutation were analyzed in 25 GBMs to evaluate its utility as a therapeutic target. Associations between the TERT promoter mutation and a number of preclinical/clinical characteristics were analyzed. Notably, the TERT promoter mutation was identified in 92.3% of GBMs where dissociated cells revealed in vitro sphere formation capacity; while the TERT promoter mutation was identified in 33.3% of GBMs without in vitro sphere formation capacity (P=0.004). In addition, this significantly increased mutation rate was observed in GBMs with in vivo tumorigenic potential (80% vs. 0%; P=0.004). Furthermore, patients with GBM exhibiting the TERT promoter mutation demonstrated significantly decreased overall survival rate compared with patients lacking this mutation (81.7 vs. 152.6 weeks; P=0.026). The results of the present study indicated that the TERT promoter mutation is associated with the self-renewal capacity of GBM cells and clinical aggressiveness of GBMs, which may be translated to a targeting therapy against TERT to inhibit the self-renewal of GBM cells.

SUBMITTER: Jeong DE 

PROVIDER: S-EPMC5755188 | biostudies-other | 2017 Dec

REPOSITORIES: biostudies-other