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Gut. 2018 Sep;67(9):1652-1662. doi: 10.1136/gutjnl-2017-315062. Epub 2018 Mar 2.

IPMNs with co-occurring invasive cancers: neighbours but not always relatives.

Author information

1
Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
2
Department of Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany.
3
Institute for Computational Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
4
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
5
Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
6
Department of Surgery, University and Hospital Trust of Verona, Verona, Italy.
7
Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
8
Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
9
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Abstract

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.

KEYWORDS:

cancer genetics; carcinogenesis; molecular genetics; mutations; pancreatic cancer

PMID:
29500184
DOI:
10.1136/gutjnl-2017-315062
[Indexed for MEDLINE]

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