Particularly in esophageal squamous cell carcinoma, deletion of TGFBR2 in mouse fibroblasts in vivo resulted in extensive genetic and epigenetic alterations, such as loss of cyclin inhibitors p15 and p16, as well as hypermethylation of the p21WAF1 promoter in surrounding epithelial cells (Fig. 1) that ultimately developed into esophageal squamous cells carcinomas [139]. The gene discussed is TGFBR2; the disease is esophageal squamous cell carcinoma.