Intraductal Papillary Mucinous Neoplasms of the Pancreas: A Review of Their Genetic Characteristics and Mouse Models

SIMPLE SUMMARY: Pancreatic cancer is one of the deadliest cancers with the lowest survival rate. Little progress has been achieved in prolonging the survival for patients with pancreatic adenocarcinoma. Hence, special attention should be paid to pre-cancerous lesions, for instance, an intraductal papillary mucinous neoplasm (IPMN). Here, we reviewed its genetic characteristics and the mouse models involving mutations in specific pathways, and updated our current perception of how this lesion develops into a precursor of invasive cancer. ABSTRACT: The intraductal papillary mucinous neoplasm (IPMN) is attracting research attention because of its increasing incidence and proven potential to progress into invasive pancreatic ductal adenocarcinoma (PDAC). In this review, we summarized the key signaling pathways or protein complexes (GPCR, TGF, SWI/SNF, WNT, and PI3K) that appear to be involved in IPMN pathogenesis. In addition, we collected information regarding all the genetic mouse models that mimic the human IPMN phenotype with specific immunohistochemistry techniques. The mouse models enable us to gain insight into the complex mechanism of the origin of IPMN, revealing that it can be developed from both acinar cells and duct cells according to different models. Furthermore, recent genomic studies describe the potential mechanism by which heterogeneous IPMN gives rise to malignant carcinoma through sequential, branch-off, or de novo approaches. The most intractable problem is that the risk of malignancy persists to some extent even if the primary IPMN is excised with a perfect margin, calling for the re-evaluation and improvement of diagnostic, pre-emptive, and therapeutic measures.