Furthermore, it would be interesting to determine whether other epigenetic events regulating chromatin organization, such as histone modifications, are also involved in the loss of Shh and whether the complex enhancer of the Shh gene, a cluster of three long-range, 840 kb regions (Lettice et al., 2003; Sagai et al., 2009), is associated with the development of urothelial carcinoma. The gene discussed is SHH; the disease is urothelial carcinoma.