GNAS Mutations in Concomitant Pancreatic Ductal Adenocarcinoma: A Pilot Study
Ladan Fazlollahi, Dora Dias-Santagata, Klaus Sahora, Vicente Morales-Oyarvide, Lindsay A Bernardo, Anthony J Iafrate, Martha B Pitman, Carlos Fernandez-del Castillo, Mari Mino-Kenudson. Massachusetts General Hospital, Boston, MA
Background: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a cystic precursor lesion of infiltrating pancreatic adenocarcinoma. KRAS mutations occur frequently in both IPMN and pancreatic intraepithelial neoplasia (PanIN). Recent reports demonstrated that GNAS mutations are prevalent in IPMN, especially in the intestinal type (IPMN-I), as well as invasive carcinoma derived from IPMN (invasive IPMN), but GNAS mutations are rare (up to 7%) in PanIN lesions and are absent in conventional pancreatic ductal adenocarcinoma (PDAC) that does not have any association with IPMN. However, GNAS mutations have not been evaluated in PDAC that is seen as a separate focus in the pancreas with IPMN (concomitant PDAC).
Design: The study cohort consisted of 23 IPMN lesions from 23 subjects consisting of 5 IPMN-I lesions (2 branch-duct and 3 mixed types; all intermediate-grade dysplasia) and 18 gastric-type IPMNs (IPMN-G; all branch-duct type; low- to intermediate-grade dysplasia). The latter included 4 with concomitant PDACs and 1 with invasive IPMN. GNAS and KRAS mutation assays using a SNaPshot platform were performed in 23 intraductal components and 5 invasive carcinomas.
Results: GNAS mutations were identified in 10 (56%) IPMN-G, and 4 (80%) IPMN-I, and KRAS mutations in 15 (83%) IPMN-G and 1 (20%) IPMN-I. Nine (50%) IPMN-G and 1 (20%) IPMN-I harbored concurrent KRAS and GNAS mutations. Interestingly, 2 concomitant PDACs harbored concurrent KRAS and GNAS mutations while the corresponding IPMN lesions only showed KRAS mutations. One concomitant PDAC harbored a KRAS mutation only while the corresponding IPMN showed both KRAS and GNAS mutations. The remaining concomitant PDAC and invasive IPMN and their corresponding intraductal components only showed KRAS mutations.
Conclusions: The results of this pilot study confirm that GNAS mutations are more prevalent in IPMN-I than in IPMN-G, and suggest that the genetic signature of concomitant PDAC may have overlap with that of IPMN and may be different from that of conventional PDAC (without any association with IPMN). A larger scale study is underway.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 171, Tuesday Afternoon