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?

Dorothee Gramatzki; Jörg Felsberg; Bettina Hentschel; Marietta Wolter; Gabriele Schackert; Manfred Westphal; Luca Regli; Niklas Thon; Marcos Tatagiba; Wolfgang Wick; Uwe Schlegel; Dietmar Krex; Jakob Matschke; Patrick Roth; Marian P Suresh; Marcel A Kamp; Elisabeth J Rushing; Torsten Pietsch; Andreas von Deimling; Michael Sabel; Markus Loeffler; Michael Weller; Guido Reifenberger

doi:10.1016/j.ejca.2021.01.014

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?

Standard

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? / Gramatzki, Dorothee; Felsberg, Jörg; 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; von Deimling, Andreas; Sabel, Michael; Loeffler, Markus; Weller, Michael; Reifenberger, Guido.

In: EUR J CANCER, Vol. 147, 04.2021, p. 84-94.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Gramatzki, D, Felsberg, J, Hentschel, B, Wolter, M, Schackert, G, Westphal, M, Regli, L, Thon, N, Tatagiba, M, Wick, W, Schlegel, U, Krex, D, Matschke, J, Roth, P, Suresh, MP, Kamp, MA, Rushing, EJ, Pietsch, T, von Deimling, A, Sabel, M, Loeffler, M, Weller, M & Reifenberger, G 2021, '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?', EUR J CANCER, vol. 147, pp. 84-94. https://doi.org/10.1016/j.ejca.2021.01.014

APA

Gramatzki, D., Felsberg, J., Hentschel, B., Wolter, M., Schackert, G., Westphal, M., Regli, L., Thon, N., Tatagiba, M., Wick, W., Schlegel, U., Krex, D., Matschke, J., Roth, P., Suresh, M. P., Kamp, M. A., Rushing, E. J., Pietsch, T., von Deimling, A., ... Reifenberger, G. (2021). 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? EUR J CANCER, 147, 84-94. https://doi.org/10.1016/j.ejca.2021.01.014

Vancouver

Gramatzki D, Felsberg J, Hentschel B, Wolter M, Schackert G, Westphal M et al. 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? EUR J CANCER. 2021 Apr;147:84-94. https://doi.org/10.1016/j.ejca.2021.01.014

Bibtex

@article{c39e381feb6b4add917f9b3f2166a6cc,

title = "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?",

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 O6-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 D{\"u}sseldorf, Germany, and Zurich, Switzerland (n = 302).RESULTS: In the GGN cohort, but not in the D{\"u}sseldorf/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.",

author = "Dorothee Gramatzki and J{\"o}rg Felsberg and Bettina Hentschel and Marietta Wolter and Gabriele Schackert and Manfred Westphal and Luca Regli and Niklas Thon and Marcos Tatagiba and Wolfgang Wick and Uwe Schlegel and Dietmar Krex and Jakob Matschke and Patrick Roth and Suresh, {Marian P} and Kamp, {Marcel A} and Rushing, {Elisabeth J} and Torsten Pietsch and {von Deimling}, Andreas and Michael Sabel and Markus Loeffler and Michael Weller and Guido Reifenberger",

year = "2021",

month = apr,

doi = "10.1016/j.ejca.2021.01.014",

language = "English",

volume = "147",

pages = "84--94",

journal = "EUR J CANCER",

issn = "0959-8049",

publisher = "Elsevier Limited",

}

RIS

TY - JOUR

T1 - 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?

AU - Gramatzki, Dorothee

AU - Felsberg, Jörg

AU - Hentschel, Bettina

AU - Wolter, Marietta

AU - Schackert, Gabriele

AU - Westphal, Manfred

AU - Regli, Luca

AU - Thon, Niklas

AU - Tatagiba, Marcos

AU - Wick, Wolfgang

AU - Schlegel, Uwe

AU - Krex, Dietmar

AU - Matschke, Jakob

AU - Roth, Patrick

AU - Suresh, Marian P

AU - Kamp, Marcel A

AU - Rushing, Elisabeth J

AU - Pietsch, Torsten

AU - von Deimling, Andreas

AU - Sabel, Michael

AU - Loeffler, Markus

AU - Weller, Michael

AU - Reifenberger, Guido

PY - 2021/4

Y1 - 2021/4

N2 - 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 O6-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 Düsseldorf, Germany, and Zurich, Switzerland (n = 302).RESULTS: 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.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.

AB - 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 O6-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 Düsseldorf, Germany, and Zurich, Switzerland (n = 302).RESULTS: 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.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.

U2 - 10.1016/j.ejca.2021.01.014

DO - 10.1016/j.ejca.2021.01.014

M3 - SCORING: Journal article

C2 - 33631540

VL - 147

SP - 84

EP - 94

JO - EUR J CANCER

JF - EUR J CANCER

SN - 0959-8049

ER -