A 58-year-old man presents with progressive headache, cognitive decline, and a single seizure. MRI brain shows a ring-enhancing mass crossing the corpus callosum (marked **A**), with central necrosis and extensive perilesional edema. Histopathology confirms a WHO Grade 4 astrocytoma. Which of the following molecular markers is MOST critical for predicting response to temozolomide-based chemotherapy in this patient?
A. MGMT promoter methylation status
B. EGFR amplification
C. IDH1/IDH2 mutation status
D. TERT promoter mutation
Explanation
Why MGMT promoter methylation status is right
MGMT (O⁶-methylguanine-DNA methyltransferase) methylation is the single most predictive biomarker for temozolomide (TMZ) response in glioblastoma multiforme. Patients with MGMT-methylated tumors show significantly improved survival with TMZ-based chemoradiation compared to unmethylated tumors. This is a core component of the WHO 2021 CNS classification and is essential for prognostication and treatment planning in GBM, particularly for the ring-enhancing mass crossing the corpus callosum shown as structure A (Stupp et al. NEJM 2005; WHO CNS Classification 2021).
Why each distractor is wrong
IDH1/IDH2 mutation status: While IDH status distinguishes GBM-IDH-wildtype (adult-type, common) from IDH-mutant astrocytoma Grade 4 (younger, better prognosis), it does NOT predict TMZ response. IDH status is a prognostic classifier, not a chemotherapy predictor.
EGFR amplification: EGFR amplification is a common finding in GBM and is part of the molecular signature, but it does not predict TMZ response. It may guide targeted therapy decisions (e.g., EGFR inhibitors) in recurrent disease, not initial chemotherapy.
TERT promoter mutation: TERT promoter mutations are frequent in GBM and contribute to the molecular profile, but they are not predictive of TMZ sensitivity. TERT status is prognostic but not chemotherapy-predictive.
High-YieldNEET PG
MGMT methylation = TMZ benefit; IDH status = prognosis & tumor classification; EGFR/TERT = molecular signature but not chemo-predictive.
WHO CNS Classification 2021; Stupp et al. NEJM 2005; NCCN Guidelines CNS Cancers
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