The following is a summary of “A systematic review of high impact CpG sites and regions for MGMT methylation in glioblastoma [A systematic review of MGMT methylation in GBM],” published in the March 2024 issue of Neurology by Gibson et al.
Researchers conducted a retrospective study to assess the impact of MGMT promoter methylation testing variability on prognostic evaluation in glioblastoma (GBM).
They conducted comprehensive searches in PubMed, Web of Science, and Embase and scrutinized 2,925 article abstracts to identify significant MGMT promoter CpG sites. The GRADE scoring system was utilized to evaluate bias risk and study quality.
The results showed that 15 articles met the inclusion criteria for adult GBM, focusing on MGMT promoter sites or regions related to overall survival, progression-free survival, and/or MGMT expression. Systematic reviews and articles on lower-grade glioma were excluded. Pyrosequencing or BeadChip arrays were commonly used, with CpG sites between CpG’s 70–90 receiving the most attention. Moderate concordance was observed among highly predictive CpG sites for prognosis. Combinations or means of sites between CpG’s 73–89 were linked to improved overall and progression-free survival. Six studies identified CpG sites closer to the transcription start site (CpG’s 8, 19, 22, 25, 27, 32, 38) and CpG sites 21–37, along with low methylation levels in enhancer regions, as associated with prognosis.
Investigators concluded that the link between MGMT promoter methylation extent and survival in GBM appears non-linear and requires further investigation of specific CpG sites and methylation patterns.
Source: bmcneurol.biomedcentral.com/articles/10.1186/s12883-024-03605-3