BRAF non-V600 mutation (Class II / Class III)
Deterministische Ansicht der Quelle YAML Entität. Klinische Autorität bleibt mit den zitierten Quell-IDs und Rezensenten Sign-off Zustand.
| ID | BIO-BRAF-CLASS-II-III |
|---|---|
| Art | Biomarker |
| Aliase | BRAF-Klasse IIBRAF-Klasse IIIBRAF D594BRAF G466BRAF G469ABRAF G469VBRAF K601EBRAF L597BRAF N581BRAF non-V600 (Class II/III)Мутація BRAF не-V600 (клас II / клас III) |
| Status | reviewed 2026-04-29 | pending_clinical_signoff |
| Erkrankungen | None declared |
| Quellen | SRC-CIVIC SRC-ESMO-NSCLC-METASTATIC-2024 SRC-NCCN-MELANOMA-2025 SRC-NCCN-NSCLC-2025 |
Biomarker-Fakten
| Biomarker-Typ | gene_mutation |
|---|---|
| Angaben zur Mutation | {"functional_impact": "Class II — RAF dimer formation independent of upstream RAS activation; intermediate kinase activity; resistant to monomer-selective Type-I RAF inhibitors (vemurafenib / dabrafenib / encorafenib alone). Class III — kinase-dead or impaired; signal via heterodimerisation with wild-type CRAF; require upstream RTK / RAS activation to drive MAPK signalling.\n", "gene": "BRAF", "gene_hugo_id": "HGNC:1097", "hotspots": ["Class II (RAS-independent dimers, intermediate-to-high kina... |
| Messung | VerfahrenDNA-NGS panel (preferred) OR ctDNA NGS. PCR hot-spot panels limited to V600 — miss non-V600. Einheitenkategorisch; Reportvariante + Klasse (II vs III) explizit SensitivitätsanforderungStandard-NGS; Tumorzellularität ≥ 20% empfohlen |
| Verwandte Biomarker | BIO-BRAF-V600E BIO-BRAF-V600K BIO-KRAS |
Anmerkungen
~5-10% of BRAF-mutant tumors overall (NSCLC, melanoma, CRC) are non-V600; proportion higher in lung adeno where Class II / Class III combined approach the V600 cohort. Distinct from V600 in BOTH biology and therapy. Class II (G469A, K601E, L597) — RAF dimer formation drives signalling; monomer-selective BRAF inhibitors fail; MEK inhibitor (trametinib / binimetinib) monotherapy may show partial activity; pan-RAF dimer inhibitors (e.g., naporafenib / belvarafenib / exarafenib, lifirafenib) in trial. Class III (D594, G466, N581) — kinase-impaired; require upstream RTK activity; treat per RTK driver if present (e.g., EGFR or KRAS-G12C co-mutation), else MEK inhibition limited rationale. CRC Class II / III almost always co-occur with RAS or other MAPK alteration — distinct from V600E CRC (which is targetable per BEACON). Practice gap: PCR-only V600 hot-spot testing misses non-V600 entirely; full BRAF-region NGS required to detect.
Verwendet von
Keine Rückverweise im YAML-Korpus gefunden.