SMAD4 and invasive carcinoma: Through whole exome and targeted sequencing analyses of 18 IPMNs/MCNs and associated invasive carcinomas, we confirmed the high prevalence of mutations in previously identified pancreatic driver genes, including mutations of KRAS (89% of cases), GNAS (28%), CDKN2A (44%), TP53 (67%), SMAD4 (50%), and TGFBR2 (17%) (Fig. 1b).