Neurosurgery notes/Tumours/Tumour genetics/MAPK pathway alterations

MAPK pathway alterations

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Parent item
Tumour genetics

Consist of

  • Receptor Tyrosine Kinases (RTKs)
    • Mutations or amplifications in EGFR, other RTKs activate upstream MAPK signaling.
  • RAS GTPases
    • Oncogenic mutations in HRAS, KRAS, NRAS (most frequent MAPK alterations) lock RAS in GTP-bound active state.
  • RAF kinases
    • BRAF mutations (e.g., V600E), fusions (e.g., KIAA1549-BRAF), CRAF alterations; class I (high activity), class II/III (impaired kinase).
  • MEK kinases
    • Mutations in MAP2K1 (MEK1), MAP2K2 (MEK2) cause constitutive activation.
  • ERK1/2
    • Rare mutations/amplifications leading to hyperactivation.
  • Other modules
    • JNK pathway (MAPK8/9/10, MAP2K4/7), p38 pathway (MAPK14/11/12/13, MAP2K3/6) mutations.
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Associated tumours

  • Pilocytic astrocytoma (pLGG, ~70% MAPK alterations: BRAF fusions, V600E, NF1).
  • Polymorphous low-grade neuroepithelial tumor of the young (PLNTY, BRAF V600E, FGFR2/3).
  • Diffuse astrocytoma, AYA-type (MAPK-altered: NF1, PTPN11, BRAF, CDKN2A/2B del).
  • Ganglioglioma, high-grade glioma (BRAF alterations).
  • Glioblastoma (GBM, p38 MAPK activation correlated with grade, invasion).
  • H3K27M-mutant diffuse midline glioma (some MAPK alterations in long survivors).
  • Diffuse low-grade glioma, MAPK pathway-altered