Germline variants in pancreatic cancer patients with a personal or family history of cancer fulfilling the revised Bethesda guidelines
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Pancreatic 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.
Among 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.
The 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.
These findings showed that these guidelines could be useful for identifying PC patients with DNA damage repair genes as well as MMR genes.
KeywordsPancreatic cancer Lynch syndrome DNA mismatch repair genes Revised Bethesda guidelines Germline variants
We wish to thank all of the patients and their families who contributed to this study. We also thank Dr. Kokichi Sugano and Dr. Teruhiko Yoshida (Department of Genetic Medicine and Services, National Cancer Center Hospital).
Compliance with ethical standards
Conflict of interest
All the authors declare no potential conflicts of interest.
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