{"entity":{"id":"paper-wu-pancreatic-cyst-exomes-rnf43-pnas-2011","kind":"paper","name":"Whole-exome sequencing of neoplastic cysts of the pancreas reveals recurrent mutations in components of ubiquitin-dependent pathways","aka":[],"tldr":"Sequencing the four main kinds of pancreatic cyst found that the two that can turn into cancer, IPMN and mucinous cystic neoplasm, share inactivating mutations in a previously unknown suppressor gene, RNF43.","summary":"Exomic sequences were determined from the neoplastic epithelium of eight surgically resected cysts of each major type: serous cystadenoma, IPMN, mucinous cystic neoplasm and solid pseudopapillary neoplasm. They contained 10, 27, 16 and 2.9 somatic mutations per tumour respectively. Four of eight serous cystadenomas carried VHL mutations. Six of eight IPMNs and three of eight mucinous cystic neoplasms harboured mutations of RNF43, a gene encoding a protein with intrinsic E3 ubiquitin ligase activity not previously found altered in any human cancer; the preponderance of inactivating mutations establishes it as a suppressor of both. Solid pseudopapillary neoplasms always contained CTNNB1 mutations.","asOf":"2026-09-24","links":[{"label":"Wu et al., PNAS 2011: exomes of neoplastic pancreatic cysts, RNF43 in IPMN and MCN","url":"https://doi.org/10.1073/pnas.1118046108"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22158988/"}],"tags":[],"related":[],"cancers":["pancreatic","ipmn-cystic-precursors"],"sections":[],"technologies":[],"targets":["rnf43","ctnnb1"],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":["wnt","ubiquitin-proteasome-system"],"terms":[],"trials":[],"people":["bert-vogelstein","kenneth-kinzler"],"bottlenecks":[],"keyPapers":[],"journals":["pnas"],"dependsOn":[],"notes":[],"journal":"PNAS","year":2011,"doi":"10.1073/pnas.1118046108","pmid":"22158988","authors":"Wu J, Jiao Y, Dal Molin M, et al.","paperType":"translational","findings":["RNF43 inactivating mutations in 6 of 8 IPMNs and 3 of 8 mucinous cystic neoplasms.","VHL in serous cystadenomas; CTNNB1 in every solid pseudopapillary neoplasm."],"whatItMeans":"It put RNF43 on the pancreatic driver list and gave cyst fluid testing a way to separate the harmless serous cyst from the mucinous ones that need watching.","caveats":["Eight cysts of each type.","Mutation profiles do not by themselves grade dysplasia."],"changedPractice":false,"participants":32},"route":"/key-papers/paper-wu-pancreatic-cyst-exomes-rnf43-pnas-2011/","neighbours":{"cancer":[{"id":"ipmn-cystic-precursors","kind":"cancer","name":"Intraductal papillary mucinous neoplasm and other pancreatic cystic precursors","route":"/cancers/ipmn-cystic-precursors/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"target":[{"id":"ctnnb1","kind":"target","name":"CTNNB1","route":"/targets/ctnnb1/"},{"id":"rnf43","kind":"target","name":"RNF43","route":"/targets/rnf43/"}],"institution":[{"id":"johns-hopkins","kind":"institution","name":"Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center","route":"/institutions/johns-hopkins/"}],"pathway":[{"id":"ubiquitin-proteasome-system","kind":"pathway","name":"Ubiquitin-proteasome system & protein homeostasis","route":"/pathways/ubiquitin-proteasome-system/"},{"id":"wnt","kind":"pathway","name":"Wnt / β-catenin","route":"/pathways/wnt/"}],"person":[{"id":"bert-vogelstein","kind":"person","name":"Bert Vogelstein","route":"/people/bert-vogelstein/"},{"id":"kenneth-kinzler","kind":"person","name":"Kenneth W. Kinzler","route":"/people/kenneth-kinzler/"}],"journal":[{"id":"pnas","kind":"journal","name":"Proceedings of the National Academy of Sciences","route":"/journals/pnas/"}]}}