These findings suggested that DNA methylation of the Shh gene functions as a molecular basis for the loss of Shh expression in invasive urothelial carcinoma and confirmed the role of Hh signaling to the stroma in the initiation of bladder cancer at the early stage of disease, as previously reported (Shin et al., 2014a; Shin et al., 2014b). The gene discussed is SHH; the disease is urinary bladder cancer.