SMAD4 and pancreatic ductal adenocarcinoma: Among driver mutations, inactivation of the SMAD4 tumor suppressor gene—a core mediator of transforming growth factor-β (TGFβ) signaling—is a hallmark of several gastrointestinal malignancies that is found at the highest frequency in pancreatic ductal adenocarcinoma (PDAC)5,9,10.