Germline Mutations in Apparent Sporadic Pancreatic Adenocarcinoma

Key Points

  • Germline mutations in known pancreatic cancer susceptibility genes were found in 3.5% of patients with pancreatic cancer who do not have a reported family history of cancer.
  • A family history of pancreatic cancer was reported for only 3 of 33 patients with these mutations.

As reported by Shindo et al in the Journal of Clinical Oncology, deleterious germline mutations in known pancreatic cancer susceptibility genes were frequently found in patients with pancreatic cancer who do not have a reported family history of cancer.

Study Details

The study involved sequencing for 32 known or candidate pancreatic susceptibility genes or other cancer susceptibility genes in DNA from normal tissue from 854 patients with pancreatic ductal adenocarcinoma, 288 patients with other pancreatic and periampullary neoplasms, and 51 patients with non-neoplastic diseases who underwent pancreatic resection at The Johns Hopkins Hospital between 2000 and 2015.

Identification of Known Susceptibility Mutations

Overall, 33 of 854 patients (3.9%) with pancreatic cancer had a deleterious germline mutation; 31 (3.5%) involved known familial pancreatic cancer susceptibility genes, including BRCA2 (12 patients), ATM (10 patients), BRCA1 (3 patients), PALB2 (2 patients), MLH1 (2 patients), CDKN2A (1 patient), and TP53 (1 patient). Patients with these mutations were younger than those without the mutations (mean age = 60.8 vs 65.1 years, P = .03). Deleterious germline mutations were also found in the candidate pancreatic cancer susceptibility genes BUB1B (one patient) and BUB3 (one patient).

A family history of pancreatic cancer was reported for only 3 of the 33 patients. Although most of the patients (82%) had a family history of other cancers, only 5 (15%) had histories suggestive of a familial cancer syndrome.

Of the 339 patients with diagnoses other than pancreatic ductal carcinoma, 5 (1.5%) had a deleterious germline mutation. Each of the 5 had another malignancy.

The investigators concluded: “Germline mutations in pancreatic cancer susceptibility genes are commonly identified in patients with pancreatic cancer without a significant family history of cancer. These deleterious pancreatic cancer susceptibility gene mutations, some of which are therapeutically targetable, will be missed if current family history guidelines are the main criteria used to determine the appropriateness of gene testing.”

The study was supported by National Institutes of Health grants, Susan Wojcicki and Dennis Troper, and Rolfe Pancreatic Cancer Foundation.

Michael Goggins, MD, of The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, is the corresponding author of the Journal of Clinical Oncology article. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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