Two types of SMO mutations were identified: mutations within or adjacent to the binding pocket that interfered with drug binding (including D473 mutant identified in a drug-resistant medulloblastoma patient [97]) and mutations outside the binding pocket, many of which confer constitutive activity to SMO (including the oncogenic W535L mutation identified in BCC [49,98,99]). This evidence concerns the gene SMO and skin basal cell carcinoma.