MAP2K1 Aktivierungsmutation (MEK1)
Deterministische Ansicht der Quelle YAML Entität. Klinische Autorität bleibt mit den zitierten Quell-IDs und Rezensenten Sign-off Zustand.
| ID | BIO-MAP2K1 |
|---|---|
| Art | Biomarker |
| Aliase | MAP2K1 / MEK1 MutationАктивуюча мутація MAP2K1 (MEK1) |
| Status | reviewed 2026-05-04 | pending_clinical_signoff |
| Erkrankungen | DIS-GLIOMA-LOW-GRADE DIS-HCL |
| Quellen | SRC-EANO-LGG-2024 SRC-NCCN-CNS-2025 |
Biomarker-Fakten
| Biomarker-Typ | gene_mutation |
|---|---|
| Angaben zur Mutation | {"exon": "2, 3 (kinase domain)", "functional_impact": "activating", "gene": "MAP2K1", "variant_type": "missense activating"} |
| Messung | VerfahrenTumor NGS-Panel; Schlüsselvarianten: K57E (~30% HCL-V), Q56P, E203K, F53L, D67N |
| Nachschlagewerk für die Aktionsfähigkeit | {"gene": "MAP2K1", "variant": "activating_mutation"} |
| Verwandte Biomarker | BIO-BRAF-V600E |
Anmerkungen
MAP2K1 (MEK1) is a dual-specificity kinase directly downstream of BRAF and upstream of ERK1/2. Activating mutations constitute an alternative mechanism of MAPK pathway activation in tumors that lack BRAF mutations. Key clinical contexts: (1) Hairy cell leukemia variant (HCL-V): MAP2K1 K57E present in ~40–50% of HCL-V cases (which are BRAF V600E-negative by definition). Cobimetinib (MEK inhibitor) shows activity in MAP2K1-mutant HCL-V in small series; no FDA approval but NCCN 2B evidence. (2) Low-grade glioma (LGG): MAP2K1 mutations are one of the MAPK pathway alterations (~5–10% of BRAF-fusion-negative LGGs). Trametinib (MEK inhibitor) shows activity in pediatric LGG with MAPK pathway alterations per FIREFLY-1 trial (binimetinib/trametinib). (3) Melanoma: MAP2K1 mutations occur in ~5–8% as secondary resistance to BRAF inhibitors; MEK inhibitors still active but combination needed. (4) Histiocytic disorders (ECD, LCH): MAP2K1 mutations as alternative to BRAF V600E. Do not confuse MEK inhibitors approved for BRAF V600E indications — those approvals are as adjuncts to BRAF inhibitors (vemurafenib + cobimetinib; dabrafenib + trametinib) and are not driven by MAP2K1 mutation status.
Verwendet von
Therapeutische Relevanz
BMA-MAP2K1-HCL- Haarzellenleukämie-Variante (HCL-V) ist ein seltenes Milz-B-Zell-Lymphom (~10% der HCL-Fälle)...BMA-MAP2K1-LGG- MAPK-Wegaktivierung ist das Markenzeichen von pädiatrischem Low-Grade-Gliom (pLGG) und Okc...