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  • GENOME-WIDE ASSOCIATION  (1)
  • 1
    Keywords: CANCER ; EXPRESSION ; TUMORS ; NERVOUS-SYSTEM ; GLIOMA ; temozolomide ; TELOMERASE ACTIVITY ; GENOME-WIDE ASSOCIATION ; SECONDARY GLIOBLASTOMAS ; PHASE-3 TRIAL
    Abstract: Background. Activating somatic mutations in the promoter region of the telomerase reverse transcriptase gene (TERT) have been detected in several cancers. In this study we investigated the TERT promoter mutations and their impact on patient survival in World Health Organization grade IV glioblastoma multiforme (GBM). Methods. The TERT core promoter region containing the previously described mutations and a common functional polymorphism (rs2853669) was sequenced in tumors and blood samples from 192 GBM patients. O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status was assessed by pyrosequencing in 177 (92.2%) cases. Relevant clinical data were obtained from a prospectively maintained electronic database. Results. We detected specific (-124 C〉T and -146 C〉T) TERT promoter mutations in 143/178 (80.3%) primary GBM and 4/14 (28.6%) secondary GBM (P〈 .001). The presence of TERT mutations was associated with poor overall survival, and the effect was confined to the patients who did not carry the variant G-allele for the rs2853669 polymorphism. An exploratory analysis suggested that TERT mutations might be prognostic only in patients who had incomplete resections and no temozolomide chemotherapy. Conclusions. In this study, specific TERT promoter mutations were markers of primary GBM and predicted patient survival in conjunction with a common functional polymorphism. The prognostic impact of TERT mutations was absent in patients with complete resections and temozolomide chemotherapy. If confirmed in additional studies, these findings may have clinical implications, that is, TERT mutations appear to characterize tumors that require aggressive treatment.
    Type of Publication: Journal article published
    PubMed ID: 25140036
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