The Significance of MGMT Promoter Methylation Status in Diffuse Glioma

Int J Mol Sci. 2022 Oct 27;23(21):13034. doi: 10.3390/ijms232113034.

Abstract

A single-institution observational study with 43 newly diagnosed diffuse gliomas defined the isocitrate dehydrogenase 1 and 2 (IDH1/2) gene mutation status and evaluated the prognostic relevance of the methylation status of the epigenetic marker O6-methylguanine-DNA methyltransferase (MGMT). Younger patients (<50 years) with surgically resected glioma and temozolomide (TMZ) adjuvant chemotherapy were associated with better prognosis, consistent with other studies. The methylation status depends on the chosen method and the cut-off value determination. Methylation-specific PCR (MSP) established the methylation status for 36 glioma patients (19 (52.8%) positively methylated and 17 (47.2%) unmethylated) without relevancy for the overall survival (OS) (p = 0.33). On the other side, real-time methylation-specific PCR (qMSP) revealed 23 tumor samples (54%) that were positively methylated without association with OS (p = 0.15). A combined MSP analysis, which included the homogenous cohort of 24 patients (>50 years with surgical resection and IDH1/2-wildtype diffuse glioma), distinguished 10 (41.6%) methylated samples from 14 (58.4%) unmethylated samples. Finally, significant correlation between OS and methylation status was noticed (p ≈ 0.05). The OS of the hypermethylated group was 9.6 ± 1.77 months, whereas the OS of the unmethylated group was 5.43 ± 1.04 months. Our study recognized the MGMT promoter methylation status as a positive prognostic factor within the described homogenous cohort, although further verification in a larger population of diffuse gliomas is required.

Keywords: IDH1; IDH2; MGMT; MSP; diffuse glioma; glioblastoma; qMSP.

Publication types

  • Observational Study

MeSH terms

  • Brain Neoplasms* / pathology
  • DNA Methylation
  • DNA Modification Methylases / genetics
  • DNA Repair Enzymes / genetics
  • Glioblastoma* / genetics
  • Glioma* / pathology
  • Humans
  • O(6)-Methylguanine-DNA Methyltransferase / genetics
  • Promoter Regions, Genetic
  • Temozolomide / therapeutic use
  • Tumor Suppressor Proteins / genetics

Substances

  • DNA Modification Methylases
  • DNA Repair Enzymes
  • Temozolomide
  • O(6)-Methylguanine-DNA Methyltransferase
  • MGMT protein, human
  • Tumor Suppressor Proteins