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

• Published in: Scientific reports 2020-11, Vol.10 (1), p.19758-19758, Article 19758
• Main Authors: Karschnia, Philipp, Teske, Nico, Dorostkar, Mario M., Siller, Sebastian, Weller, Jonathan, Baehring, Joachim M., Dietrich, Jorg, von Baumgarten, Louisa, Herms, Jochen, Tonn, Joerg-Christian, Thon, Niklas
• Format: Article
• Language: English
• Subjects: 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
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-76312-x

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.