GNAS codon 201 mutations are uncommon in intraductal papillary neoplasms of the bile duct

Abstract Background Activating point mutations of GNAS at codon 201 have been detected in approximately two thirds of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Intraductal papillary neoplasms of the bile ducts (IPNBs) morphologically resemble pancreatic IPMNs. This study sought to assess the mutational status of GNAS at codon 201 in IPNBs. Methods Thirty-four patients were included. DNA from microdissected IPNBs was subjected to a polymerase chain reaction and ligation method for the detection of GNAS mutations at codon 201 and of KRAS mutations at codon 12. Mutational status was compared with clinical and pathologic data. Results The IPNBs had a median diameter of 3.5 cm and were located intrahepatically ( n = 6), extrahepatically ( n = 13), both intra- and extrahepatically ( n = 4) or in the gallbladder (intracystic papillary neoplasms, n = 11). Most exhibited pancreatobiliary differentiation ( n = 20), high-grade dysplasia ( n = 26) and an associated adenocarcinoma ( n = 20). Analysis of GNAS codon 201 identified only one mutant sample in a multifocal intestinal subtype intrahepatic IPNB with high-grade dysplasia. Six lesions harboured a KRAS codon 12 mutation. Conclusions GNAS codon 201 mutations are uncommon in IPNBs, by contrast with pancreatic IPMNs. More comprehensive molecular profiling is needed to uncover the pathways involved in IPNB development.