Journal Article

Extent and prognostic value of MGMT promotor methylation in glioma WHO grade II

Siller, Sebastian, Baehring, Joachim M., Tonn, Joerg-Christian, Dietrich, Jorg, Karschnia, Philipp, Thon, Niklas, Teske, Nico, Herms, Jochen, von Baumgarten, Louisa, Weller, Jonathan, Dorostkar, Mario M.

2020

Overview

MGMT promotor methylation is associated with favourable outcome in high-grade glioma. In glioma WHO grade II, it is unclear whether the extent of MGMT promotor methylation and its prognostic role is independent from other molecular markers. We performed a retrospective analysis of 155 patients with glioma WHO grade II. First, all 155 patients were assigned to three molecular groups according to the 2016 WHO classification system: (1) oligodendroglioma, IDH-mutant and 1p19q co-deleted (n = 81); (2) astrocytoma, IDH-mutant and 1p19q non-codeleted (n = 54); (3) astrocytoma, IDH-wildtype (n = 20). MGMT promotor methylation was quantified using Sanger sequencing of the CpG sites 74–98 within the MGMT promotor region. Highest numbers of methylated CpG sites were found for oligodendroglioma, IDH-mutant and 1p19q co-deleted. When 1p19q co-deletion was absent, numbers of methylated CpG sites were higher in the presence of IDH-mutation. Accordingly, lowest numbers were seen in the IDH-wildtype subpopulation. In the entire cohort, larger numbers of methylated CpG sites were associated with favourable outcome. When analysed separately for the three WHO subgroups, a similar association was only retained in astrocytoma, IDH-wildtype. Collectively, extent of MGMT promotor methylation was strongly associated with other molecular markers and added prognostic information in astrocytoma, IDH-wildtype. Evaluation in prospective cohorts is warranted.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/208/176/1988 / 631/67/1922 / 692/308/53 / 692/4028/546 / 692/499 / 692/617/375 / Adult / Aged / Aged, 80 and over / Astrocytoma / Biomarkers, Tumor - genetics / Brain cancer / Combined Modality Therapy / CpG islands / DNA Methylation / DNA Modification Methylases - genetics / DNA Repair Enzymes - genetics / Female / Follow-Up Studies / Gene Expression Regulation, Neoplastic / Glioma / Glioma - genetics / Glioma - pathology / Glioma - therapy / Humanities and Social Sciences / Humans / Male / Methylation / Middle Aged / multidisciplinary / Mutants / Mutation / Neoplasm Grading / Oligodendroglioma / Promoter Regions, Genetic / Retrospective Studies / Science / Science (multidisciplinary) / Survival Rate / Tumor Suppressor Proteins - genetics