SMAD4 and neoplasm: The current model for PDAC development is that genomic alterations occur in a stepwise manner with mutations in KRAS and CDKN2A preceding in early Pan-IN lesions, which are precursor lesions for invasive carcinoma, often followed by mutations in TP53 and SMAD4 which contribute to the tumor’s invasiveness (Aguirre et al., 2003; Hingorani et al., 2005; Iacobuzio-Donahue et al., 2012; Ryan et al., 2014).