FBXW7 Funktionsverlustmutation
Deterministische Ansicht der Quelle YAML Entität. Klinische Autorität bleibt mit den zitierten Quell-IDs und Rezensenten Sign-off Zustand.
| ID | BIO-FBXW7 |
|---|---|
| Art | Biomarker |
| Aliase | FBXW7-MutationМутація втрати функції FBXW7 |
| Status | reviewed 2026-05-04 | pending_clinical_signoff |
| Erkrankungen | DIS-CRC |
| Quellen | SRC-ESMO-CRC-2024 SRC-NCCN-COLON-2025 |
Biomarker-Fakten
| Biomarker-Typ | gene_mutation |
|---|---|
| Angaben zur Mutation | {"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)"} |
| Messung | VerfahrenTumor-NGS-Panel (DNA); RNA-Seq für Expressionsverlust (Forschung) |
| Nachschlagewerk für die Aktionsfähigkeit | {"gene": "FBXW7", "variant": "loss_of_function"} |
| Verwandte Biomarker | BIO-NOTCH1 BIO-KRAS BIO-TP53 BIO-CDKN2A |
Anmerkungen
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.
Verwendet von
Therapeutische Relevanz
BMA-FBXW7-CRC- FBXW7 Funktionsverlustmutationen treten in ~10–15% der SFB auf und führen zu einer Stabilisierung von m...