Abstract 3503: Somatic mutations and aberrant expression of RNF43 are recurrently found in intraductal papillary mucinous neoplasms of the pancreas

Background: RNF43 encodes ring finger protein 43, an ubiquitin ligase, and is recently uncovered as mutated in intraductal papillary mucinous neoplasms of the pancreas (IPMNs). We studied mutations and aberrant expressions of RNF43 and their associations with molecular and clinicopathological features in IPMNs. Materials and methods: Studied were 178 IPMNs operated upon between 2001 and 2010 at Tokyo Women9s Medical University Hospital. Formalin-fixed and paraffin-embedded tissues of the 178 cases and frozen tisssues of 56 of the cases were subjected for immunohistochemical and the next generation semiconducter sequencing analyses, respectively. Detected mutations were validated by Sanger sequencing. Results: Expression of RNF43 was reduced in 60 (33.7%) of the 178 IPMNs. Somatic mutations in RNF43 were found in 10 (17.9%) of the 56 examined cases, in which frameshift mutations, a nonsense mutation, and missense mutations were found in 5, 1, and 4 cases, respectively. These mutations were significantly associated with RNF43 expression (p = 0.008) and GNAS mutation (p = 0.012), however, not associated with tumor grade, histological subtype or prognosis. Conclusion: These results indicate that RNF43 may function as a tumor suppressor and play a role in development of IPMN. Citation Format: Hitomi Sakamoto, Yuko Kuboki, Takashi Hatori, Masakazu Yamamoto, Masanori Sugiyama, Noriyuki Shibata, Kyoko Shimizu, Keiko Shiratori, Toru Furukawa. Somatic mutations and aberrant expression of RNF43 are recurrently found in intraductal papillary mucinous neoplasms of the pancreas. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3503. doi:10.1158/1538-7445.AM2014-3503