Whole-exome sequencing of neoplastic cysts of the pancreas reveals recurrent mutations in components of ubiquitin-dependent pathways

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.