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. 2022 Jun 27;14(13):3149.
doi: 10.3390/cancers14133149.

Quantitative Analysis of the MGMT Methylation Status of Glioblastomas in Light of the 2021 WHO Classification

Levin Häni  1 , Monika Kopcic  1 , Mattia Branca  2 , Alessa Schütz  1 , Michael Murek  1 , Nicole Söll  1 , Erik Vassella  3 , Andreas Raabe  1 , Ekkehard Hewer  3   4 , Philippe Schucht  1
Affiliations

Quantitative Analysis of the MGMT Methylation Status of Glioblastomas in Light of the 2021 WHO Classification

Levin Häni et al. Cancers (Basel). .

Abstract

Background: Glioblastomas with methylation of the promoter region of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene exhibit increased sensitivity to alkylating chemotherapy. Quantitative assessment of the MGMT promoter methylation status might provide additional prognostic information. The aim of our study was to determine a quantitative methylation threshold for better survival among patients with glioblastomas. Methods: We included consecutive patients ≥18 years treated at our department between 11/2010 and 08/2018 for a glioblastoma, IDH wildtype, undergoing quantitative MGMT promoter methylation analysis. The primary endpoint was overall survival. Results: A total of 321 patients were included. Median overall survival was 12.6 months. Kaplan−Meier and adjusted Cox regression analysis showed better survival for the groups with 16−30%, 31−60%, and 61−100% methylation. In contrast, survival in the group with 1−15% methylation was similar to those with unmethylated promoter regions. A secondary analysis confirmed this threshold. Conclusions: Better survival is observed in patients with glioblastomas with ≥16% methylation of the MGMT promoter region than with <16% methylation. Survival with tumors with 1−15% methylation is similar to with unmethylated tumors. Above 16% methylation, we found no additional benefit with increasing methylation.

Keywords: O(6)-methylguanine-DNA methyltransferase; glioblastoma; temozolomide.

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Conflict of interest statement

The authors declare no conflict of interest relevant to the manuscript.

Figures

Figure 1
Figure 1
Flowchart illustrating patient selection.
Figure 2
Figure 2
Kaplan-Meier analysis stratified for MGMT promoter methylation status. Patients with ≥16% methylation of the MGMT promoter region displayed significantly longer survival compared with patients with unmethylated tumors. Survival of patients with 1–15% methylation was similar to that of patients with unmethylated MGMT promotors.
Figure 3
Figure 3
Kaplan-Meier subgroup analysis of patients with low MGMT promoter methylation. Survival of patients with tumors with 1–7% and 8–15% methylation of the MGMT promoter region showed no difference and was similar to patients with unmethylated tumors. Compared with these subgroups, survival of patients with tumors with ≥16% methylation was longer.
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