Which genetic alteration is the most common molecular hallmark of glioblastoma multiforme (WHO Grade IV astrocytoma)?

Explanation

## Molecular Genetics of Glioblastoma **Key Point:** EGFR amplification and/or mutation is the most frequent genetic alteration in primary glioblastoma multiforme (GBM), occurring in 30–50% of cases. ### Glioblastoma Molecular Subtypes | Genetic Alteration | Frequency | Grade | Prognosis | Notes | |---|---|---|---|---| | EGFR amplification/mutation | 30–50% | IV (GBM) | Poor | Most common in primary GBM | | TP53 mutation | 20–30% | III–IV | Poor | Associated with secondary GBM pathway | | IDH1/IDH2 mutation | 5–10% | IV | Relatively better | Defines "IDH-mutant" GBM (better prognosis) | | 1p/19q co-deletion | Rare in GBM | II–III (oligodendroglioma) | Better | Hallmark of oligodendroglioma, NOT GBM | **High-Yield:** EGFR amplification is a hallmark of **primary (de novo) glioblastoma**, which arises without a lower-grade precursor. In contrast, **secondary glioblastoma** (arising from lower-grade glioma) more often harbors TP53 mutations and IDH mutations. **Clinical Pearl:** IDH-mutant GBMs have a significantly better prognosis than IDH-wildtype GBMs, and IDH mutation status is now a WHO 2021 diagnostic criterion for glioma classification. **Mnemonic:** **EGFR-GBM** — EGFR is the most common driver in Grade IV astrocytoma (GBM).