A 60-year-old man undergoes craniotomy for a right temporal glioblastoma (GBM). Post-operatively, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status is reported as methylated. Per EORTC-NCIC and subsequent trials, what is the significance of MGMT methylation in GBM treatment?
- A MGMT-methylated GBM responds better to temozolomide chemotherapy due to impaired DNA repair in tumor cells ✓
- B MGMT-methylated GBM has worse prognosis and requires higher dose temozolomide
- C MGMT methylation predicts bevacizumab response rather than temozolomide response
- D MGMT methylation is only relevant in low-grade gliomas, not GBM
Explanation
MGMT (O6-methylguanine-DNA methyltransferase) is a DNA repair enzyme that removes the alkyl groups added to guanine by temozolomide, allowing tumor cells to survive chemotherapy. When the MGMT promoter is methylated (epigenetically silenced), the enzyme is not expressed, leaving tumor cells unable to repair alkylation damage — making them sensitive to temozolomide. EORTC-NCIC 26981 trial established that Stupp protocol (radiation + temozolomide) improved survival in GBM overall, with MGMT methylation being the strongest predictive biomarker for benefit. Median OS with methylated MGMT is 21+ months vs 12–14 months in unmethylated GBM with the same treatment.
Reference: Bailey & Love's Short Practice of Surgery, 27th ed.
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Written and medically reviewed by the StethoPrep medical team.