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

来源：

EUROPEAN JOURNAL OF CANCER | 2021年 / 147卷

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

页码：84 / 94

页数：11

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