MAP2K1 ativando a mutação (MEK1)
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| ID | BIO-MAP2K1 |
|---|---|
| Tipo | Biomarcador |
| Alegais | MAP2K1 / mutação MEK1Активуюча мутація MAP2K1 (MEK1) |
| Estado | reviewed 2026-05-04 | pending_clinical_signoff |
| Doenças | DIS-GLIOMA-LOW-GRADE DIS-HCL |
| Fontes | SRC-EANO-LGG-2024 SRC-NCCN-CNS-2025 |
Fatos de biomarcadores
| Tipo de biomarcador | gene_mutation |
|---|---|
| Detalhes da mutação | {"exon": "2, 3 (dominio de kinase)", "functional_impact":"activando", "gene":", "MAP2K1", "variant_type": |
| Medição | MétodoPanel NGS tumor; variantes chave: K57E (~30% de HCL-V), Q56P, E203K, F53L, D67N |
| Procura de ação | {"gene": "MAP2K1", "variant": "activating_mutation"} |
| Biomarcadores relacionados | BIO-BRAF-V600E |
Notas
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.
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