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Background  To clarify the genetic mutations associated with intraductal papillary mucinous neoplasms (IPMN) and IPMN-related pancreatic tumours, we conducted cancer-related gene profiling analyses using pure pancreatic juice and resected pancreatic tissues.    Methods  Pure pancreatic juice was collected from 152 patients [nine with a normal pancreas, 22 with chronic pancreatitis (CP), 39 with pancreatic ductal adenocarcinoma (PDAC), and 82 with IPMN], and resected tissues from the pancreas were collected from 48 patients (six IPMNs and 42 PDACs). The extracted DNA was amplified by multiplexed polymerase chain reaction (PCR) targeting 46 cancer-related genes containing 739 mutational hotspots. The mutations were analysed using a semiconductor-based DNA sequencer.    Results  Among the 46 cancer-related genes,  KRAS  and  GNAS  mutations were most frequently detected in both PDAC and IPMN cases. In pure pancreatic juice,  GNAS  mutations were detected in 7.7% of PDAC cases and 41.5% of IPMN cases ( p <0.001 vs. others). All PDAC cases with  GNAS  mutations (n = 3) were accompanied by IPMN. Multivariate analysis revealed that  GNAS  mutations in IPMN cases were associated with dilated main pancreatic ducts (MPD,  p  = 0.016), while no statistically independent associations with clinical variables were observed for  KRAS  mutations. In the resected pancreatic tissues,  GNAS  mutations were detected in 50% of PDAC cases concomitant with IPMN, 33.3% of PDAC cases derived from IPMN, and 66.7% of IPMN cases, while no  GNAS  mutations were detected in cases of PDAC without IPMN.    Conclusions  The  GNAS  mutation was specifically found in the cases with IPMN and it was speculated that some PDACs might be influenced by the concomitant but separately-located IPMN in their pathogenic mechanism. Furthermore, the  GNAS  mutation was significantly associated with MPD dilatation in IPMN cases, suggesting its role in mucus hypersecretion.

plos one

Deep Sequencing of Cancer-Related Genes Revealed GNAS Mutations to Be Associated with Intraductal Papillary Mucinous Neoplasms and Its Main Pancreatic Duct Dilation