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Gastroenterology. 2019 Feb 1. pii: S0016-5085(19)30353-1. doi: 10.1053/j.gastro.2019.01.254. [Epub ahead of print]

Prevalence of Germline Mutations Associated with Cancer Risk in Patients With Intraductal Papillary Mucinous Neoplasms.

Author information

1
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
2
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Medical Oncology, Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, China.
3
The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
4
Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
5
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
6
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
7
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
8
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.
9
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
10
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Electronic address: nrobert8@jhmi.edu.

Abstract

BACKGROUND & AIMS:

Many patients with pancreatic adenocarcinoma (PDAC) carry germline mutations associated with increased risk of cancer. It is not clear whether patients with intraductal papillary mucinous neoplasms (IPMNs), which are precursors to some pancreatic cancers, also carry these mutations. We assessed the prevalence of germline mutations associated with cancer risk in patients with histologically confirmed IPMN.

METHODS:

We obtained non-tumor tissue from 315 patients with surgically resected IPMNs, from 1997 through 2017, and sequenced 94 genes with variants associated with cancer risk. Mutations associated with increased risk of cancer were identified and compared to individuals from the Exome Aggregation Consortium.

RESULTS:

We identified 23 patients with a germline mutation associated with cancer risk (7.3%; 95% CI, 4.9%-10.8%). Nine patients had a germline mutation associated with pancreatic cancer susceptibility (2.9% 95% CI, 1.4%-5.4%). More patients with IPMNs carried germline mutations in ATM (P<.0001), PTCH1 (P<.0001), and SUFU (P<.0001) compared with controls. Patients with IPMNs and germline mutations associated with pancreatic cancer were more like to have concurrent invasive pancreatic carcinoma compared to patients with IPMNs without these mutations (P<.0320).

CONCLUSIONS:

In sequence analyses of 315 patients with surgically resected IPMNs, we found almost 3% to carry mutations associated with pancreatic cancer risk. More patients with IPMNs and germline mutations associated with pancreatic cancer had concurrent invasive pancreatic carcinoma compared to patients with IPMNs without these mutations. Genetic analysis of patients with IPMNs might identify those at greatest risk for cancer.

KEYWORDS:

Pancreas; cancer; genetics; predisposition

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