Somatic mutations in GNAS are frequently found in intraductal papillary mucinous neoplasms (IPMNs) of pancreas, and have been identified in 41% to 66% of cases. All of these mutations involved codon 201 (R201C or R201H). However, the GNAS mutation was infrequent in typical pancreatic ductal adenocarcinomas (PDAs). These mutations are lead to disruption of the intrinsic hydrolytic activity of Gsα, leading to constitutive activation. GNAS mutations seem to be an early event in IPMN development. The clinical significance of these mutations remains to be established.