Mutação de perda de função FBXW7
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| ID | BIO-FBXW7 |
|---|---|
| Tipo | Biomarcador |
| Alegais | Mutação FBXW7Мутація втрати функції FBXW7 |
| Estado | reviewed 2026-05-04 | pending_clinical_signoff |
| Doenças | DIS-CRC |
| Fontes | SRC-ESMO-CRC-2024 SRC-NCCN-COLON-2025 |
Fatos de biomarcadores
| Tipo de biomarcador | gene_mutation |
|---|---|
| Detalhes da mutação | {"exon": "multiple; hotspot arginine triad R465, R479, R505 in WD40 substrate-recognition domain", "functional_impact": "loss-of-function (impaired ubiquitin-mediated degradation of oncoproteins: NOTCH1/2, MYC, CCNE1, mTOR, JUN, MCL-1)", "gene": "FBXW7", "variant_type": "loss-of-function (missense at Arg triad, frameshift, nonsense)"} |
| Medição | MétodoPanel NGS tumoral (ADN); RNA-seq para perda de expressão (investigação) |
| Procura de ação | {"gene": "FBXW7", "variant": "loss_of_function"} |
| Biomarcadores relacionados | BIO-NOTCH1 BIO-KRAS BIO-TP53 BIO-CDKN2A |
Notas
FBXW7 (F-Box and WD Repeat Domain Containing 7) is the substrate-recognition subunit of the SCF (SKP1-CUL1-F-box) E3 ubiquitin ligase complex. FBXW7 recognizes phosphodegrons on multiple oncoproteins and mediates their ubiquitin-proteasomal degradation. Key substrates: NOTCH1/2, MYC, CCNE1, mTOR, JUN, MCL-1. Loss of FBXW7 → stabilization of these oncoproteins → resistance to multiple targeted therapies. Frequency: ~10–15% CRC (one of highest across cancers), ~15% T-ALL, ~6% gastric, ~5% pancreatic. Clinical significance: FBXW7 mutation is a resistance mechanism (to anti-NOTCH, CDK4/6i via CCNE1 upregulation, mTOR inhibitors via mTOR stabilization) rather than an independent therapeutic target. In CRC, FBXW7 mutation does not select any approved systemic therapy; it may co-occur with MSI-H (favoring immunotherapy) but is not independently actionable. ESCAT IV.
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Relevância terapêutica
BMA-FBXW7-CRC- As mutações de perda de função do FBXW7 ocorrem em ~10–15% do CRC e resultam na estabilização de m...