Telomerase reverse transcriptase promoter mutation- and O

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

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Déclaration de conflit d'intérêts

Conflict of interest statement P.R. has received honoraria for advisory board participation and lectures from Bristol-Myers Squibb (BMS), Debiopharm, Medac, Merck, MSD, Novocure, QED and Roche. T.P. has received honoraria for lectures from Chugai, Tokyo, and Mayo Clinic, Rochester. M.S. has received honoraria for consulting from Novocure and Integra. Mi.W. has received research grants from AbbVie, Adastra, Dracen, Merck Sharp & Dohme (MSD), Merck (EMD) and Novocure and honoraria for lectures or advisory board participation or consulting from AbbVie, Basilea, BMS, Celgene, Medac, MSD, Merck (EMD), Nerviano Medical Sciences, Orbus, Roche and Tocagen. G.R. has received honoraria for advisory board participations from AbbVie. The other authors report no disclosures.