PTCH1 and cancer: Ligand-independent HH pathway activation as a result of mutations in genes encoding upstream pathway components, such as loss-of-function mutations in PTCH1 or SUFU (suppressor of fused) and activating mutations of SMO are rare in cancers and only found in cutaneous basal cell carcinoma, rhabdomyosarcoma, and medulloblastoma, cancers which exhibit notable therapeutic response to HH inhibitors11.