SMAD4 and pancreatic ductal adenocarcinoma: For instance, human pancreatic ductal adenocarcinoma (PDAC) is characterized besides the common K-Ras mutations (representing an early event in PDAC tumourigenesis) by both TGF-βoverexpression and mutational inactivation of the tumour suppressor Smad4/DPC4, the latter being a relatively late event.