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Epigenetic evolution of isocitrate dehydrogenase-wildtype glioblastomas
Bo Deng1, Rania Head1, Kaspar Draaisma2
1Department of Neurology, Erasmus MC Cancer institute, University Medical Center, Rotterdam, The Netherlands.
Neuro-Oncology
|January 4, 2026
Summary
The DNA methylation patterns in IDH-wildtype glioblastomas remain largely stable during tumor progression. While MGMT promoter demethylation can occur, it is infrequent and associated with poorer patient survival outcomes.
Area of Science:
- Neuro-oncology
- Epigenetics
- Cancer Genomics
Background:
- Limited research exists on the epigenetic evolution of IDH-wildtype glioblastomas.
- MGMT promoter demethylation is a potential mechanism for treatment resistance.
Purpose of the Study:
- To investigate the epigenetic stability of IDH-wildtype glioblastomas during tumor progression.
- To analyze changes in MGMT promoter methylation status and their impact on patient survival.
Main Methods:
- Whole genome DNA methylation data from 418 IDH-wildtype glioblastoma samples (primary and recurrent).
- MGMT promoter methylation analysis using the MGMT-STP27 algorithm.
- Survival analysis using CoxPH regression.
Main Results:
- The methylome of IDH-wildtype glioblastomas is highly stable (93%) at progression.
- MGMT promoter conversion from methylated to unmethylated status occurred in 13.6% of cases and was linked to worse survival.
- Few differentially methylated CpGs were found between MGMT methylated and unmethylated tumors, primarily within the MGMT gene body.
Conclusions:
- The DNA methylome is generally stable throughout IDH-wildtype glioblastoma progression.
- Changes in MGMT promoter methylation status are infrequent but clinically significant, impacting patient outcomes.
