90% of sporadic BCC cases carry somatic mutations in Ptch, others have gain of-function mutations in Smo, leading to over-activation of the pathway.327,328 Overexpression of Ptch1 and Gli1 were observed in BCC compared with normal epidermal tissue and enhanced Shh immunoexpression was found in the aggressive BCC.329,330 Interestingly, Gli1 was specifically upregulated in BCC, while the other skin malignancies such as squamous cell carcinoma showed no Gli1 expression.331. Here, SMO is linked to skin basal cell carcinoma.