Next, in light of our earlier findings that concomitant inactivation of Prdm16 was able to shift the evolution of the IPMN-to-PDAC phenotype in KSC mice toward the PanIN-to-PDAC phenotype, we wondered whether ablation of TβRII or Smad4 could differentially affect the nature of the premalignant lesions leading to PDAC, and if so, whether this event depends on Prdm16. The gene discussed is SMAD4; the disease is pancreatic intraductal papillary-mucinous neoplasm.