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 gutjnl-2017-315062
DO 10.1136/gutjnl-2017-315062
A1 Matthäus Felsenstein
A1 Michaël Noë
A1 David L Masica
A1 Waki Hosoda
A1 Peter Chianchiano
A1 Catherine G Fischer
A1 Gemma Lionheart
A1 Lodewijk A A Brosens
A1 Antonio Pea
A1 Jun Yu
A1 Georgios Gemenetzis
A1 Vincent P Groot
A1 Martin A Makary
A1 Jin He
A1 Matthew J Weiss
A1 John L Cameron
A1 Christopher L Wolfgang
A1 Ralph H Hruban
A1 Nicholas J Roberts
A1 Rachel Karchin
A1 Michael G Goggins
A1 Laura D Wood
YR 2018
UL http://gut.bmj.com/content/early/2018/03/02/gutjnl-2017-315062.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.