SMAD4 and pancreatic intraductal papillary-mucinous neoplasm: Genetic alterations in IPMN have been identified, including mutations in the K-RAS (Z’Graggen et al, 1997; Schönleben et al, 2007), SMAD4 (Hruban et al, 2004), TP53 (Sessa et al, 1994) and PIK3CA genes (Schönleben et al, 2006), and have been shown to activate the mitogen-activated protein kinase and phosphatidylinositol-3 kinase pathways (Sessa et al, 1994; Semba et al, 2003).