SHH and urothelial carcinoma: Interestingly, recent large-scale genomic studies in human bladder cancer (Cancer Genome Atlas Research Network, 2014a) have revealed that mutations of genes involved in epigenetic regulation are highly enriched in invasive urothelial carcinomas, while an extensive analysis by our group showed no mutational changes in the SHH gene; these results raise the possibility that epigenetic activities may be responsible for the loss of SHH expression during the initiation of urothelial carcinomas.