Akihiro Ohmoto1, Chigusa Morizane2, Emi Kubo3, Erina Takai1, Hiroko Hosoi3, Yasunari Sakamoto3, Shunsuke Kondo3, Hideki Ueno3, Kazuaki Shimada4, Shinichi Yachida1,5, Takuji Okusaka3. 1. Laboratory of Clinical Genomics, National Cancer Center Research Institute, Tokyo, Japan. 2. Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 1040045, Japan. cmorizan@ncc.go.jp. 3. Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 1040045, Japan. 4. Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan. 5. Department of Cancer Genome Informatics, Graduate School of Medicine/Faculty of Medicine, Osaka University, Osaka, Japan.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: These findings showed that these guidelines could be useful for identifying PC patients with DNA damage repair genes as well as MMR genes.
BACKGROUND:Pancreatic cancer (PC) is categorized as a neoplasm associated with Lynch syndrome; however, the precise proportion of PCpatients harboring DNA mismatch repair genes (MMR genes) remains unclear, especially in the Asian population. METHODS: 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. RESULTS: 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. CONCLUSIONS: These findings showed that these guidelines could be useful for identifying PCpatients with DNA damage repair genes as well as MMR genes.
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