Differential elevation of TERT activity and sensitivity to temozolomide by type of TERT mutation in MGMT promoter-methylated glioblastoma.

2018 
2013Background: Benefit from temozolomide chemotherapy in glioblastoma is essentially limited to patients with tumors with O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. The impact of the MGMT status on chemosensitivity may be modulated by telomerase reverse transcriptase (TERT) promoter mutations which affect two regions of the TERT promoter, designated as C228T and C250T. Methods: TERT promoter mutation status and TERT activity were determined in a panel of glioma cell lines and correlated with sensitivity to irradiation or temozolomide. TERT status alterations were induced using sh-mediated gene TERT silencing or wildtype TERT overexpression. TERT mutation and MGMT promoter methylation status were also determined in a clinical patient cohort from the German Glioma Network. Results: C228T-mutant glioma cell lines (n = 8) express higher levels of TERT mRNA (mean 0.046±0.012 vs 0.012±0.004 arbitrary units, p = 0.049) and exhibit higher TERT catalytic activity (mean 122±16 vs 53±11 arb...
    • Correction
    • Source
    • Cite
    • Save
    • Machine Reading By IdeaReader
    0
    References
    0
    Citations
    NaN
    KQI
    []