RNF43 Mutations in IPMN Cases: A Potential Prognostic Factor

An intraductal papillary mucinous neoplasm (IPMN) is a common pancreatic precursor lesion, and it often harbors mutations inKRAS,GNAS, andRNF43. To clarify the molecular profiles of IPMNs, we conducted mutation analysis ofKRAS,GNAS, andRNF43in 61 IPMN formalin-fixed, paraffin-embedded (FFPE) specimens. The mutation rates of codons 12, 13, and 61 inKRASand codon 201 inGNASwere detected by Sanger sequencing. Next-generation sequencing was performed onRNF43, and the results were further verified by Sanger sequencing. We identifiedKRASandGNASmutations in 35 (57%) and 40 (66%) IPMN cases, respectively.GNASmutations were significantly correlated with the morphologic subtype (P<0.001) and were more prevalent in the intestinal subtype (93%) than in the gastric (55%) and pancreatobiliary subtypes (44%) but were absent in the oncocytic subtype.RNF43mutations were found in 5 cases (8%), all of which occurred in high-grade dysplasia and invasive lesions (2/5 and 3/5). All 5 cases harboring RNF43 mutations also exhibited GNAS mutations. RNF43 mutations were associated with a worse prognosis in invasive IPMN patients (P=0.002), while KRAS and GNAS mutations did not affect the prognosis of patients.