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?

被引:12
作者
Gramatzki, Dorothee [1 ,2 ]
Felsberg, Joerg [3 ]
Hentschel, Bettina [4 ]
Wolter, Marietta [3 ]
Schackert, Gabriele [5 ]
Westphal, Manfred [6 ]
Regli, Luca [2 ,7 ]
Thon, Niklas [8 ]
Tatagiba, Marcos [9 ]
Wick, Wolfgang [10 ,11 ]
Schlegel, Uwe [12 ]
Krex, Dietmar [5 ]
Matschke, Jakob [13 ]
Roth, Patrick [1 ,2 ]
Suresh, Marian P. [14 ]
Kamp, Marcel A. [14 ]
Rushing, Elisabeth J. [2 ,15 ]
Pietsch, Torsten [16 ]
von Deimling, Andreas [17 ,18 ,19 ]
Sabel, Michael [14 ]
Loeffler, Markus [4 ]
Weller, Michael [1 ,2 ]
Reifenberger, Guido [3 ,20 ]
机构
[1] Univ Hosp, Dept Neurol, Zurich, Switzerland
[2] Univ Zurich, Zurich, Switzerland
[3] Heinrich Heine Univ, Med Fac, Inst Neuropathol, Dusseldorf, Germany
[4] Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany
[5] Univ Dresden, Dept Neurosurg, Dresden, Germany
[6] Univ Hamburg, Dept Neurosurg, Hamburg, Germany
[7] Univ Hosp, Dept Neurosurg, Zurich, Switzerland
[8] Ludwig Maximilians Univ Munchen, Dept Neurosurg, Munich, Germany
[9] Univ Tubingen, Interdisciplinary Div Neurooncol, Dept Neurosurg, Tubingen, Germany
[10] Univ Hosp Heidelberg, Dept Neurol, Heidelberg, Germany
[11] German Canc Res Ctr, German Canc Consortium DKTK, Clin Cooperat Unit Neurooncol, Heidelberg, Germany
[12] Ruhr Univ Bochum, Univ Hosp Knappschaftskrankenhaus, Dept Neurol, Bochum, Germany
[13] Univ Hamburg, Inst Neuropathol, Hamburg, Germany
[14] Heinrich Heine Univ, Med Fac, Dept Neurosurg, Dusseldorf, Germany
[15] Univ Hosp, Dept Neuropathol, Zurich, Switzerland
[16] Univ Hosp Bonn, DGNN Brain Tumor Reference Ctr, Dept Neuropathol, Bonn, Germany
[17] Univ Hosp Heidelberg, Dept Neuropathol, Heidelberg, Germany
[18] German Canc Ctr DKFZ, CCU Neuropathol, Heidelberg, Germany
[19] German Canc Ctr DKFZ, DKTK, Heidelberg, Germany
[20] German Canc Res Ctr, German Canc Consortium, Partner Site Essen Dusseldorf, Heidelberg, Germany
关键词
Glioblastoma; IDH-; wild-type; MGMT; TERT; Temozolomide; Survival; GLIOMAS; MGMT; TUMORS; CLASSIFICATION; RADIOTHERAPY; COMBINATION; DIAGNOSIS; GENES; OCCUR;
D O I
10.1016/j.ejca.2021.01.014
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:84 / 94
页数:11
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