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Prognostic or predictive value of MGMT promoter methylation in gliomas depends on IDH1 mutation

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Prognostic or predictive value of MGMT promoter methylation in gliomas depends on IDH1 mutation. / Wick, Wolfgang; Meisner, Christoph; Hentschel, Bettina; Platten, Michael; Schilling, Alissa; Wiestler, Benedikt; Sabel, Michael C; Koeppen, Susanne; Ketter, Ralf; Weiler, Markus; Tabatabai, Ghazaleh; von Deimling, Andreas; Gramatzki, Dorothee; Westphal, Manfred; Schackert, Gabriele; Loeffler, Markus; Simon, Matthias; Reifenberger, Guido; Weller, Michael.

in: NEUROLOGY, Jahrgang 81, Nr. 17, 22.10.2013, S. 1515-22.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Wick, W, Meisner, C, Hentschel, B, Platten, M, Schilling, A, Wiestler, B, Sabel, MC, Koeppen, S, Ketter, R, Weiler, M, Tabatabai, G, von Deimling, A, Gramatzki, D, Westphal, M, Schackert, G, Loeffler, M, Simon, M, Reifenberger, G & Weller, M 2013, 'Prognostic or predictive value of MGMT promoter methylation in gliomas depends on IDH1 mutation', NEUROLOGY, Jg. 81, Nr. 17, S. 1515-22. https://doi.org/10.1212/WNL.0b013e3182a95680

APA

Wick, W., Meisner, C., Hentschel, B., Platten, M., Schilling, A., Wiestler, B., Sabel, M. C., Koeppen, S., Ketter, R., Weiler, M., Tabatabai, G., von Deimling, A., Gramatzki, D., Westphal, M., Schackert, G., Loeffler, M., Simon, M., Reifenberger, G., & Weller, M. (2013). Prognostic or predictive value of MGMT promoter methylation in gliomas depends on IDH1 mutation. NEUROLOGY, 81(17), 1515-22. https://doi.org/10.1212/WNL.0b013e3182a95680

Vancouver

Wick W, Meisner C, Hentschel B, Platten M, Schilling A, Wiestler B et al. Prognostic or predictive value of MGMT promoter methylation in gliomas depends on IDH1 mutation. NEUROLOGY. 2013 Okt 22;81(17):1515-22. https://doi.org/10.1212/WNL.0b013e3182a95680

Bibtex

@article{c8e651ccf5634d5fbecb443887a78cb4,
title = "Prognostic or predictive value of MGMT promoter methylation in gliomas depends on IDH1 mutation",
abstract = "OBJECTIVE: To explore whether the isocitrate dehydrogenase 1 (IDH1) or 1p/19q status determines the prognostic vs predictive role of O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation in the Neuro-Oncology Working Group of the German Cancer Society (NOA)-04 trial anaplastic glioma biomarker cohort.METHODS: Patients (n = 183) of the NOA-04 trial with known MGMT and IDH1 status were analyzed for interdependency of the prognostic vs predictive role of MGMT promoter methylation from IDH1 or 1p/19q status and treatment, using progression-free survival (PFS) as an endpoint. An independent validation cohort of the German Glioma Network (n = 75) and the NOA-08 trial (n = 34) served as a confirmation cohort.RESULTS: In tumors with IDH1 mutation, MGMT promoter methylation was associated with prolonged PFS with chemotherapy ± radiotherapy (RT) or RT-only groups, and is thus prognostic. In tumors without IDH1 mutation, MGMT promoter methylation was associated with increased PFS in patients treated with chemotherapy, but not in those who received RT alone as the first-line treatment, and is thus chemotherapy-predictive. In contrast, 1p/19q codeletions showed no such association with the prognostic vs predictive value of MGMT.CONCLUSIONS: MGMT promoter methylation is a predictive biomarker for benefit from alkylating agent chemotherapy in patients with IDH1-wild-type, but not IDH1-mutant, malignant gliomas of World Health Organization grades III/IV. Combined IDH1/MGMT assessment may help to individualize clinical decision-making in neuro-oncology.",
keywords = "Adult, Aged, Aged, 80 and over, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 19, DNA Methylation, DNA Modification Methylases, DNA Repair Enzymes, Female, Genetic Markers, Glioma, Humans, Isocitrate Dehydrogenase, Male, Middle Aged, Predictive Value of Tests, Prognosis, Promoter Regions, Genetic, Randomized Controlled Trials as Topic, Tumor Suppressor Proteins, Young Adult",
author = "Wolfgang Wick and Christoph Meisner and Bettina Hentschel and Michael Platten and Alissa Schilling and Benedikt Wiestler and Sabel, {Michael C} and Susanne Koeppen and Ralf Ketter and Markus Weiler and Ghazaleh Tabatabai and {von Deimling}, Andreas and Dorothee Gramatzki and Manfred Westphal and Gabriele Schackert and Markus Loeffler and Matthias Simon and Guido Reifenberger and Michael Weller",
year = "2013",
month = oct,
day = "22",
doi = "10.1212/WNL.0b013e3182a95680",
language = "English",
volume = "81",
pages = "1515--22",
journal = "NEUROLOGY",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "17",

}

RIS

TY - JOUR

T1 - Prognostic or predictive value of MGMT promoter methylation in gliomas depends on IDH1 mutation

AU - Wick, Wolfgang

AU - Meisner, Christoph

AU - Hentschel, Bettina

AU - Platten, Michael

AU - Schilling, Alissa

AU - Wiestler, Benedikt

AU - Sabel, Michael C

AU - Koeppen, Susanne

AU - Ketter, Ralf

AU - Weiler, Markus

AU - Tabatabai, Ghazaleh

AU - von Deimling, Andreas

AU - Gramatzki, Dorothee

AU - Westphal, Manfred

AU - Schackert, Gabriele

AU - Loeffler, Markus

AU - Simon, Matthias

AU - Reifenberger, Guido

AU - Weller, Michael

PY - 2013/10/22

Y1 - 2013/10/22

N2 - OBJECTIVE: To explore whether the isocitrate dehydrogenase 1 (IDH1) or 1p/19q status determines the prognostic vs predictive role of O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation in the Neuro-Oncology Working Group of the German Cancer Society (NOA)-04 trial anaplastic glioma biomarker cohort.METHODS: Patients (n = 183) of the NOA-04 trial with known MGMT and IDH1 status were analyzed for interdependency of the prognostic vs predictive role of MGMT promoter methylation from IDH1 or 1p/19q status and treatment, using progression-free survival (PFS) as an endpoint. An independent validation cohort of the German Glioma Network (n = 75) and the NOA-08 trial (n = 34) served as a confirmation cohort.RESULTS: In tumors with IDH1 mutation, MGMT promoter methylation was associated with prolonged PFS with chemotherapy ± radiotherapy (RT) or RT-only groups, and is thus prognostic. In tumors without IDH1 mutation, MGMT promoter methylation was associated with increased PFS in patients treated with chemotherapy, but not in those who received RT alone as the first-line treatment, and is thus chemotherapy-predictive. In contrast, 1p/19q codeletions showed no such association with the prognostic vs predictive value of MGMT.CONCLUSIONS: MGMT promoter methylation is a predictive biomarker for benefit from alkylating agent chemotherapy in patients with IDH1-wild-type, but not IDH1-mutant, malignant gliomas of World Health Organization grades III/IV. Combined IDH1/MGMT assessment may help to individualize clinical decision-making in neuro-oncology.

AB - OBJECTIVE: To explore whether the isocitrate dehydrogenase 1 (IDH1) or 1p/19q status determines the prognostic vs predictive role of O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation in the Neuro-Oncology Working Group of the German Cancer Society (NOA)-04 trial anaplastic glioma biomarker cohort.METHODS: Patients (n = 183) of the NOA-04 trial with known MGMT and IDH1 status were analyzed for interdependency of the prognostic vs predictive role of MGMT promoter methylation from IDH1 or 1p/19q status and treatment, using progression-free survival (PFS) as an endpoint. An independent validation cohort of the German Glioma Network (n = 75) and the NOA-08 trial (n = 34) served as a confirmation cohort.RESULTS: In tumors with IDH1 mutation, MGMT promoter methylation was associated with prolonged PFS with chemotherapy ± radiotherapy (RT) or RT-only groups, and is thus prognostic. In tumors without IDH1 mutation, MGMT promoter methylation was associated with increased PFS in patients treated with chemotherapy, but not in those who received RT alone as the first-line treatment, and is thus chemotherapy-predictive. In contrast, 1p/19q codeletions showed no such association with the prognostic vs predictive value of MGMT.CONCLUSIONS: MGMT promoter methylation is a predictive biomarker for benefit from alkylating agent chemotherapy in patients with IDH1-wild-type, but not IDH1-mutant, malignant gliomas of World Health Organization grades III/IV. Combined IDH1/MGMT assessment may help to individualize clinical decision-making in neuro-oncology.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Chromosomes, Human, Pair 1

KW - Chromosomes, Human, Pair 19

KW - DNA Methylation

KW - DNA Modification Methylases

KW - DNA Repair Enzymes

KW - Female

KW - Genetic Markers

KW - Glioma

KW - Humans

KW - Isocitrate Dehydrogenase

KW - Male

KW - Middle Aged

KW - Predictive Value of Tests

KW - Prognosis

KW - Promoter Regions, Genetic

KW - Randomized Controlled Trials as Topic

KW - Tumor Suppressor Proteins

KW - Young Adult

U2 - 10.1212/WNL.0b013e3182a95680

DO - 10.1212/WNL.0b013e3182a95680

M3 - SCORING: Journal article

C2 - 24068788

VL - 81

SP - 1515

EP - 1522

JO - NEUROLOGY

JF - NEUROLOGY

SN - 0028-3878

IS - 17

ER -