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

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.

Molecular heterogeneity and commonalities in pancreatic cancer precursors with gastric and intestinal phenotype

“…[32][33][34] So far, most functional data have focused on acinar-ductal metaplasia and PanIN formation and progression. While several mouse models have been reported to elicit different subtypes of IPMN by combining the KC or KPC mouse 35 36 with genetic targeting of additional pathways, such as the G-protein coupled receptor (GPCR) (guanine nucleotide binding protein, alpha stimulating (GNAS)), tranforming growth factor-alpha (TGFα), SWItch/ Sucrose Non-Fermentable (SWI/SNF), Wingless/Integrated (WNT) Wand phosphoinosotide-3 kinase (PI3K) pathways, 37 the functional role of Notch signalling in the development of gastric and intestinal IPMN is not well-defined. Our finding suggests that Notch signalling is selectively involved in gastric but not in intestinal precursor development.…”

A Case of a gastropancreatic fistula in the setting of intraductal papillary mucinous neoplasms

“…Colloid carcinoma has an overall better prognosis 4 , 10] . Advances in genetics have allowed clinicians to better understand the pathogenesis behind this malignant transformation [11] . Additionally, advances in technology over the last two decades have allowed clinicians to diagnose and treat IPMN's with the use of MRCP, ERCP, endoscopic ultrasound, but also allows for surveillance for malignant transformation [5 , 7] .…”

Modern aspects of the management of pancreatic intraductal papillary mucinous neoplasms: a narrative review

“…However, 12 genes were altered significantly, and the so-called “12-gene signature” has been proposed as a potential biomarker in the pancreatic juice for the identification of IPMNs that have a high risk for malignant development [ 26 ]. The key signaling pathways or protein complexes involved in the pathogenesis of IPMNs include G-protein-coupled receptor (GPCR), transforming growth factor (TGF), SWI/SNF, WNT and phosphatidylinositol 3-kinase (PI3K) [ 27 ]. A polymorphic variant in telomere maintenance is related to the appearance of worrisome features (WF) and high-risk stigmata (HRS).…”

“…The key signaling pathways or protein complexes involved in the pathogenesis of IPMNs include G-proteincoupled receptor (GPCR), transforming growth factor (TGF), SWI/SNF, WNT and phosphatidylinositol 3-kinase (PI3K) [27].…”