Telomerase reverse transcriptase promoter mutation– and O6-methylguanine DNA methyltransferase promoter methylation–mediated sensitivity to temozolomide in isocitrate dehydrogenase–wild-type glioblastoma: is there a link?

AbstractAim of the study Benefit from temozolomide (TMZ) chemotherapy in treatment isocitrate dehydrogenase (IDH)–wild-type glioblastoma is essentially limited to patients with O6-methylguanine DNA methyltransferase (MGMT) promoter–methylated tumours. Recent studies suggested that telomerase reverse transcriptase (TERT) promoter hotspot mutations may have an impact on prognostic role MGMT status glioblastoma. Methods methylation and TERT mutation were retrospectively assessed a prospective cohort IDH–wild-type German Glioma Network (GGN) (n = 298) independent retrospective Düsseldorf, Germany, Zurich, Switzerland 302). Results In GGN cohort, but not Düsseldorf/Zurich was moderately associated inferior outcomes promoter–unmethylated tumours (hazard ratio 1.74; 95% confidence interval: 1.07–2.82; p 0.026). better either cohort. The two different (C228T C250T) linked distinct outcomes. Conclusions Analysis cohorts did confirm previous data, suggesting confer enhanced benefit TMZ Thus, diagnostic testing for be required prediction sensitivity