Glioblastoma Genome

A complex and heterogeneous genomic profile characterizes glioblastoma (GBM).

• TP53 — Tumor suppressor gene; commonly mutated.
• EGFR — Often amplified or mutated (e.g., *EGFRvIII* variant).
• PTEN — Mutations/deletions → PI3K/AKT pathway activation.
• IDH1/IDH2 — Mutated in secondary GBM, better prognosis.
• TERT promoter — Mutated in primary GBM → ↑ telomerase.
• NF1 — Inactivation seen in mesenchymal subtype.
• PIK3CA / PIK3R1 — Activates PI3K pathway.

• +Chromosome 7 / -Chromosome 10 — Hallmark alteration.
• CDKN2A/B deletion — Affects p16INK4a and p14ARF (cell cycle).
• MDM2 amplification — Inhibits p53 function.

• MGMT promoter methylation — Increases sensitivity to temozolomide.
• G-CIMP phenotype — IDH1-related, associated with better survival.

• EGFR amplification
• CDKN2A deletion
• No TP53 mutation

• NF1 deletion/mutation
• High expression of CHI3L1, MET

• IDH1 mutation
• PDGFRA amplification
• TP53 mutation

• Expression of neuron-specific genes (e.g., NEFL, GABRA1)
• *Note: classification debated*

• RTK/RAS/PI3K Pathway
  • EGFR, PDGFRA, PIK3CA, NF1
• TP53 Pathway
  • TP53, MDM2
• RB Pathway
  • CDKN2A/B, RB1

• The Cancer Genome Atlas Research Network. (2008). Comprehensive genomic characterization defines human glioblastoma genes and core pathways.
• Brennan et al., Cell, 2013.
• Verhaak et al., Cancer Cell, 2010.