Loss of SMAD4 expression limited to invasive carcinomas has been reported in MCN- and IPMN-associated invasive cancers, and targeted sequencing of a small number of IPMNs and matched cancers identified a single case with a SMAD4 mutation occurring only in the cancer7,28,29. This evidence concerns the gene SMAD4 and pancreatic intraductal papillary-mucinous neoplasm.