PTCH1 loss-of-function mutation (Patched-1)
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BIO-PTCH1 |
|---|---|
| Type | Biomarker |
| Aliases | PTCH1 mutationВтрата функції PTCH1 (Patched-1) |
| Status | reviewed 2026-05-04 | pending_clinical_signoff |
| Diseases | None declared |
| Sources | SRC-NCCN-SKIN-2025 |
Biomarker Facts
| Biomarker type | gene_mutation |
|---|---|
| Mutation details | {"exon": "multiple", "functional_impact": "loss-of-function", "gene": "PTCH1", "variant_type": "loss-of-function (frameshift, nonsense, splice, missense inactivating)"} |
| Measurement | MethodTumor NGS panel; germline testing for Gorlin syndrome (pathogenic PTCH1 variant in blood) |
| Actionability lookup | {"gene": "PTCH1", "variant": "loss_of_function"} |
| Related biomarkers | BIO-SMO |
Notes
PTCH1 (Patched-1) is the primary tumor suppressor in the Hedgehog (HH) pathway. It normally inhibits SMO by sequestering it; when HH ligand (SHH, DHH, IHH) binds PTCH1, this inhibition is released, allowing SMO to activate GLI1/2 transcription factors. Somatic PTCH1 loss is the dominant driver of sporadic BCC (~90%). Germline PTCH1 mutation causes Gorlin syndrome (Basal Cell Nevus Syndrome): multiple BCCs from early adulthood, odontogenic keratocysts, skeletal anomalies, calcified falx cerebri, and markedly increased medulloblastoma risk (SHH-subtype, predominantly desmoplastic, in childhood). Gorlin syndrome patients are exquisitely sensitive to ionizing radiation (radiation-induced BCCs within field); radiation therapy is relatively contraindicated for BCC treatment in Gorlin patients. Therapeutic implication: loss of PTCH1 in BCC justifies hedgehog inhibitor (vismodegib/sonidegib) for locally advanced/metastatic disease — routine tumor PTCH1 testing is not required because HH pathway activation is universal in BCC.
Used By
Actionability
BMA-PTCH1-BCC- PTCH1 loss is the primary molecular driver of BCC (~90% of sporadic cases and all Gorlin...
Biomarker
BIO-SMO- SMO activating mutation (Smoothened)
Diseases
DIS-BCC- Basal cell carcinoma (BCC)
Indications
IND-BCC-1L-VISMODEGIB- IND-BCC-1L-VISMODEGIB