RT Journal Article SR Electronic T1 IPMNs with co-occurring invasive cancers: neighbours but not always relatives JF Gut JO Gut FD BMJ Publishing Group Ltd and British Society of Gastroenterology SP 1652 OP 1662 DO 10.1136/gutjnl-2017-315062 VO 67 IS 9 A1 Felsenstein, Matthäus A1 Noë, Michaël A1 Masica, David L A1 Hosoda, Waki A1 Chianchiano, Peter A1 Fischer, Catherine G A1 Lionheart, Gemma A1 Brosens, Lodewijk A A A1 Pea, Antonio A1 Yu, Jun A1 Gemenetzis, Georgios A1 Groot, Vincent P A1 Makary, Martin A A1 He, Jin A1 Weiss, Matthew J A1 Cameron, John L A1 Wolfgang, Christopher L A1 Hruban, Ralph H A1 Roberts, Nicholas J A1 Karchin, Rachel A1 Goggins, Michael G A1 Wood, Laura D YR 2018 UL http://gut.bmj.com/content/67/9/1652.abstract AB Objective Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions that can give rise to invasive pancreatic carcinoma. Although approximately 8% of patients with resected pancreatic ductal adenocarcinoma have a co-occurring IPMN, the precise genetic relationship between these two lesions has not been systematically investigated.Design We analysed all available patients with co-occurring IPMN and invasive intrapancreatic carcinoma over a 10-year period at a single institution. For each patient, we separately isolated DNA from the carcinoma, adjacent IPMN and distant IPMN and performed targeted next generation sequencing of a panel of pancreatic cancer driver genes. We then used the identified mutations to infer the relatedness of the IPMN and co-occurring invasive carcinoma in each patient.Results We analysed co-occurring IPMN and invasive carcinoma from 61 patients with IPMN/ductal adenocarcinoma as well as 13 patients with IPMN/colloid carcinoma and 7 patients with IPMN/carcinoma of the ampullary region. Of the patients with co-occurring IPMN and ductal adenocarcinoma, 51% were likely related. Surprisingly, 18% of co-occurring IPMN and ductal adenocarcinomas were likely independent, suggesting that the carcinoma arose from an independent precursor. By contrast, all colloid carcinomas were likely related to their associated IPMNs. In addition, these analyses showed striking genetic heterogeneity in IPMNs, even with respect to well-characterised driver genes.Conclusion This study demonstrates a higher prevalence of likely independent co-occurring IPMN and ductal adenocarcinoma than previously appreciated. These findings have important implications for molecular risk stratification of patients with IPMN.