A 55-year-old man has a contrast-enhancing ring lesion in the white matter on MRI. Biopsy shows necrotic centre with pseudopalisading of tumour cells around it. MGMT promoter methylation status is determined. Methylation of the MGMT promoter is clinically significant because it predicts:

• A Sensitivity to EGFR tyrosine kinase inhibitors
• B Resistance to bevacizumab (anti-VEGF therapy)
• C IDH1 mutation status
• D Improved response to alkylating chemotherapy (temozolomide) and better prognosis ✓

Explanation

Glioblastoma (WHO grade 4) with pseudopalisading necrosis is the most common primary brain malignancy in adults. MGMT (O6-methylguanine-DNA methyltransferase) is a DNA repair enzyme that removes alkyl adducts from O6-guanine, counteracting temozolomide's cytotoxic effect. Methylation of the MGMT promoter silences MGMT expression, preventing repair of temozolomide-induced DNA damage, thus predicting better response to alkylating agents and improved survival. MGMT methylation does not directly indicate IDH status or EGFR sensitivity.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.