SMO activant la mutation (Lisse)
Vue déterministe de l'entité source de la LJAM. L'autorité clinique demeure avec les ID de la source cités et l'état d'approbation de l ́examinateur.
| ID | BIO-SMO |
|---|---|
| Type | Biomarqueur |
| Alias | SMO mutationАктивуюча мутація SMO (Smoothened) |
| État | reviewed 2026-05-04 | pending_clinical_signoff |
| Maladies | DIS-BCC |
| Sources | SRC-ESMO-SARCOMA-2024 SRC-NCCN-SKIN-2025 |
Données biomarqueurs
| Type de biomarqueur | gene_mutation |
|---|---|
| Détails de la mutation | {"exon": "multiple", "functional_impact":"activation", "gene": «SMO», "variant_type": „missense activation"} |
| Mesure | MéthodePanneaux NGS tumoraux (basés sur l'ADN); variantes communes: W535L, L412F, Q477E, S533N |
| Recherche de la faisabilité | {"gene": "SMO", "variant": "activating_mutation"} |
| Biomarqueurs connexes | BIO-PTCH1 |
Notes
SMO (Smoothened) is a G-protein-coupled receptor that transmits Hedgehog (HH) signaling. Normally suppressed by PTCH1; activated when PTCH1 loses its inhibitory function (whether via PTCH1 loss-of-function or SMO gain-of-function mutation). SMO activating mutations (~10–20% of BCCs) and PTCH1 loss-of-function (~90% of BCCs) both result in constitutive HH pathway activation. Vismodegib and sonidegib are SMO antagonists — they bind the SMO transmembrane domain and block downstream HH signaling (GLI1/2 repression). In practice, BCC HHI therapy does not require pre-testing for SMO vs PTCH1 mutation — all BCCs have HH pathway activation. SMO mutations also occur in sporadic medulloblastoma (SHH subtype) and rarely in other tumors. Resistance: secondary SMO mutations (D473H most common) emerge during vismodegib therapy, driving acquired resistance. Sonidegib may be active in some vismodegib-resistant D473H mutants.
Utilisé par
Pertinence thérapeutique
BMA-SMO-BCC- Inhibiteurs de la voie hedgehog (HH) - vismodegib (Erivedge, FDA 2012) et sonidegib (Odomzo,...
Biomarqueur
BIO-PTCH1- mutation de la perte de fonction du PTCH1 (Patched-1)
Maladie
DIS-BCC- Carcinome à cellules basales (BCC)
Indication
IND-BCC-1L-SONIDEGIB- IND-BCC-1L-SONIDEGIB