Amplifications detected in GLI1 and DHH may assume gain of function effects, whereas, for missense mutations, we can only hypothesize inactivating alterations for the negative regulators PTCH1, PTCH2, and SUFU on one hand, and activating alterations for GLI transcription factors, SMO and Hedgehog ligands, on the other, as occurs in other types of cancer [85,125,126,127,128,129,130,131,132]. The gene discussed is SMO; the disease is cancer.