TY - JOUR
T1 - IPMNs with co-occurring invasive cancers
T2 - Neighbours but not always relatives
AU - Felsenstein, Matthaüs
AU - Noë, Michaël
AU - Masica, David L.
AU - Hosoda, Waki
AU - Chianchiano, Peter
AU - Fischer, Catherine G.
AU - Lionheart, Gemma
AU - Brosens, Lodewijk A.A.
AU - Pea, Antonio
AU - Yu, Jun
AU - Gemenetzis, Georgios
AU - Groot, Vincent P.
AU - Makary, Martin A.
AU - He, Jin
AU - Weiss, Matthew J.
AU - Cameron, John L.
AU - Wolfgang, Christopher L.
AU - Hruban, Ralph H.
AU - Roberts, Nicholas J.
AU - Karchin, Rachel
AU - Goggins, Michael G.
AU - Wood, Laura D.
N1 - Publisher Copyright:
© 2018 Article author(s).
PY - 2018/9/1
Y1 - 2018/9/1
N2 - 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.
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.
KW - cancer genetics
KW - carcinogenesis
KW - molecular genetics
KW - mutations
KW - pancreatic cancer
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U2 - 10.1136/gutjnl-2017-315062
DO - 10.1136/gutjnl-2017-315062
M3 - Article
C2 - 29500184
AN - SCOPUS:85049168458
SN - 0017-5749
VL - 67
SP - 1652
EP - 1662
JO - Gut
JF - Gut
IS - 9
ER -