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Germline variants in pancreatic cancer patients with a personal or family history of cancer fulfilling the revised Bethesda guidelines

Authors
  • Ohmoto, Akihiro1
  • Morizane, Chigusa2
  • Kubo, Emi2
  • Takai, Erina1
  • Hosoi, Hiroko2
  • Sakamoto, Yasunari2
  • Kondo, Shunsuke2
  • Ueno, Hideki2
  • Shimada, Kazuaki3
  • Yachida, Shinichi1, 4
  • Okusaka, Takuji2
  • 1 National Cancer Center Research Institute, Laboratory of Clinical Genomics, Tokyo, Japan , Tokyo (Japan)
  • 2 National Cancer Center Hospital, Department of Hepatobiliary and Pancreatic Oncology, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 1040045, Japan , Tokyo (Japan)
  • 3 National Cancer Center Hospital, Department of Hepatobiliary and Pancreatic Surgery, Tokyo, Japan , Tokyo (Japan)
  • 4 Osaka University, Department of Cancer Genome Informatics, Graduate School of Medicine/Faculty of Medicine, Osaka, Japan , Osaka (Japan)
Type
Published Article
Journal
Journal of Gastroenterology
Publisher
Springer Japan
Publication Date
Apr 17, 2018
Volume
53
Issue
10
Pages
1159–1167
Identifiers
DOI: 10.1007/s00535-018-1466-y
Source
Springer Nature
Keywords
License
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Abstract

BackgroundPancreatic cancer (PC) is categorized as a neoplasm associated with Lynch syndrome; however, the precise proportion of PC patients harboring DNA mismatch repair genes (MMR genes) remains unclear, especially in the Asian population.MethodsAmong 304 Japanese patients with pathologically proven pancreatic ductal adenocarcinoma, we selected 20 (6.6%) patients with a personal or family history involving first- or second-degree relatives fulfilling the revised Bethesda guidelines (RBG), defined as RBG-compatible cases. We analyzed germline variants in 21 genes related to a hereditary predisposition for cancer as well as clinical features in all 20 cases.ResultsThe RBG-compatible cases did not show any unique clinicopathological features. Targeted sequencing data revealed three patients carrying deleterious or likely deleterious variants. Specifically, these three patients harbored a nonsense variant in ATM, a frameshift variant in ATM, and a concurrent nonsense variant in PMS2 and missense variant in CHEK2 (double-mutation carrier), respectively. Although an MMR gene mutation was identified in only one of the 20 patients, up to 15% of the RBG-compatible PC cases were associated with germline deleterious or likely deleterious variants.ConclusionsThese findings showed that these guidelines could be useful for identifying PC patients with DNA damage repair genes as well as MMR genes.

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