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, Vol. 81, No. 17, 22.10.2013, p. 1515-22.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -