La perte de PTCH1 est le principal moteur moléculaire de la BCC (~90% des cas sporadiques et tous les...
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 | BMA-PTCH1-BCC |
|---|---|
| Type | Pertinence thérapeutique |
| État | reviewed 2026-05-04 | pending_clinical_signoff | actionability review required |
| Maladies | DIS-BCC |
| Sources | SRC-NCCN-SKIN-2025 |
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| Biomarqueur | BIO-PTCH1 |
|---|---|
| Variante | PTCH1 loss-of-function (somatic — sporadic BCC; germline — Gorlin/Basal Cell Nevus Syndrome); activates HH pathway via SMO disinhibition |
| Maladie | DIS-BCC |
| Niveau ESCAT | IA |
| Combinaisons recommandées | vismodegib 150 mg PO QD (voir BMA-SMO-BCC pour les détails complets du régime), sonidegib 200 mg POQD avec des aliments, cemiplimab 350 mg IV q3w (post-HHI), syndrome de Gorlin : surveillance multidisciplinaire (dermatologie, ophtalmologie, neurologie, génétique); vismodégib pour les CBC à charge élevée avec stratégie de rupture de toxicité |
| Résumé des faits | PTCH1 loss is the primary molecular driver of BCC (~90% of sporadic cases and all Gorlin syndrome-associated BCCs). Loss of PTCH1 function disinhibits SMO, constitutively activating Hedgehog (HH) signaling. Therapeutic implication is identical to SMO-mutant BCC: SMO antagonists (vismodegib, sonidegib) block SMO activity downstream of PTCH1 and restore HH pathway suppression. FDA approvals for vismodegib (2012) and sonidegib (2015) for laBCC/mBCC apply regardless of whether the underlying driver is PTCH1 loss or SMO mutation — clinical eligibility is based solely on disease extent (locally advanced or metastatic) and surgical/radiation suitability, not on molecular testing. Gorlin syndrome (germline PTCH1): same therapeutic approach but radiation therapy is relatively contraindicated (radiation-induced BCC within field). Cemiplimab FDA-approved post-HHI (2021). See BMA-SMO-BCC for full efficacy data (ERIVANCE, BOLT trials) — the PTCH1 and SMO BMA entries share identical therapeutic recommendations; the distinction is clinically relevant for resistance mechanism (secondary SMO mutatio... |
Notes
ESCAT IA (cross-reference BMA-SMO-BCC for primary efficacy citations). The PTCH1 BMA exists separately from SMO BMA because: (1) Gorlin syndrome patients require specific management considerations (radiation avoidance, genetic counseling, enhanced surveillance); (2) PTCH1 germline testing should be offered to BCC patients with early onset (<30y), multiple synchronous BCCs, or family history; (3) acquired HHI resistance mechanism in PTCH1-driven BCC involves secondary SMO mutation (not amplification of PTCH1). Distinguish: PTCH1 somatic (sporadic BCC — most common) vs PTCH1 germline (Gorlin — rare, ~1/30,000 live births, accounts for ~1% of all BCC cases but nearly 100% of childhood BCCs). Gorlin syndrome workup: cranial MRI (calcified falx cerebri, medulloblastoma risk), orthopantomogram (odontogenic keratocysts), skeletal survey, ophthalmology.
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