Telomerase reverse transcriptase promoter mutation- and O-6-methylguanine DNA methyltransferase promoter methylation-mediated sensitivity to temozolomide in isocitrate dehydrogenase-wild-type glioblastoma: is there a link?

Gramatzki, Dorothee; Felsberg, Joerg; Hentschel, Bettina; Wolter, Marietta; Schackert, Gabriele; Westphal, Manfred; Regli, Luca; Thon, Niklas; Tatagiba, Marcos; Wick, Wolfgang; Schlegel, Uwe; Krex, Dietmar; Matschke, Jakob; Roth, Patrick; Suresh, Marian P.; Kamp, Marcel A.; Rushing, Elisabeth J.; Pietsch, Torsten; Deimling, Andreas von; Sabel, Michael; Loeffler, Markus; Weller, Michael und Reifenberger, Guido (2021): Telomerase reverse transcriptase promoter mutation- and O-6-methylguanine DNA methyltransferase promoter methylation-mediated sensitivity to temozolomide in isocitrate dehydrogenase-wild-type glioblastoma: is there a link? In: European Journal of Cancer, Bd. 147: S. 84-94

Abstract

Aim of the study: Benefit from temozolomide (TMZ) chemotherapy in the treatment of isocitrate dehydrogenase (IDH)-wild-type glioblastoma is essentially limited to patients with O-6-methylguanine DNA methyltransferase (MGMT) promoter-methylated tumours. Recent studies suggested that telomerase reverse transcriptase (TERT) promoter hotspot mutations may have an impact on the prognostic role of the MGMT status in patients with glioblastoma. Methods: 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 Dusseldorf, Germany, and Zurich, Switzerland (n = 302). Results: In the GGN cohort, but not in the Dusseldorf/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. Conclusions: 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. (C) 2021 The Authors. Published by Elsevier Ltd.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0959-8049
• Sprache: Englisch