It has been shown that loss of members of the TGFβ signaling cascade, such as Smad4 and β2 spectrin, can contribute to the initiation of Barrett's esophagus and the progression to esophageal adenocarcinoma through concomitant upregulation of Notch targets Hes1 and Jagged1 [2]. The gene discussed is SMAD4; the disease is esophageal adenocarcinoma.