TP53 and glioblastoma: For secondary GBM, there is adistinct succession of genetic events and the course is longer:initially, activation of signal transduction pathways, usuallythrough overexpression of PDGF, PDGFR, FGF2 (instead of EGFR);p53 mutation, CDK4 amplification, Rb (retinoblastoma gene) lossand eventually, loss of PTEN unleashes the Akt pathway, leadingto downstream activation of mTOR (mammalian target of rapamycin) andother genes (NF–kB, an important transcription factorpromoting proliferation; GSK3; anti–apoptotic genes such asBAD etc.)with devastating consequences[16].