{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T15:46:24Z","timestamp":1785599184107,"version":"3.56.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2019,6,20]],"date-time":"2019-06-20T00:00:00Z","timestamp":1560988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100003645","name":"National Cancer Center","doi-asserted-by":"publisher","award":["23-A-8,\u00a025-A-5"],"award-info":[{"award-number":["23-A-8,\u00a025-A-5"]}],"id":[{"id":"10.13039\/501100003645","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003645","name":"National Cancer Center","doi-asserted-by":"publisher","award":["25-A-6"],"award-info":[{"award-number":["25-A-6"]}],"id":[{"id":"10.13039\/501100003645","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Industrial Disease Clinical Research Grants","award":["14040101-01"],"award-info":[{"award-number":["14040101-01"]}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K10674"],"award-info":[{"award-number":["17K10674"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Recently identified occupational cholangiocarcinoma among printing workers is characterized by chronic bile duct injuries and precancerous or early cancerous lesions at multiple sites of the bile ducts. These observations suggested the potential multifocal carcinogenesis of the disease. We performed whole-exome analysis of multiple lesions, including the invasive carcinomas and precancerous lesions of four occupational cholangiocarcinoma cases. A much higher mutation burden was observed in both the invasive carcinomas (mean 76.3\/Mb) and precancerous lesions (mean 71.8\/Mb) than in non-occupational cholangiocarcinomas (mean 1.6\/Mb). Most somatic mutations identified in 11 of 16 lesions did not overlap with each other. In contrast, a unique trinucleotide mutational signature of GpCpY to GpTpY was shared among the lesions. These results suggest that most of these lesions are multiclonal in origin and that common mutagenic processes, which may be induced by exposure to haloalkanes or their metabolites, generated somatic mutations at different sites of the bile ducts. A similarly high mutation rate had already been identified in the precancerous lesions, implying an increased potential for carcinogenesis throughout the biliary tree. These genomic features support the importance of ongoing close follow-up of the patients as a group at high risk of recurrence.<\/jats:p>","DOI":"10.1093\/carcin\/bgz120","type":"journal-article","created":{"date-parts":[[2019,6,19]],"date-time":"2019-06-19T11:10:09Z","timestamp":1560942609000},"page":"368-376","source":"Crossref","is-referenced-by-count":14,"title":["Multifocal origin of occupational cholangiocarcinoma revealed by comparison of multilesion mutational profiles"],"prefix":"10.1093","volume":"41","author":[{"given":"Sachiyo","family":"Mimaki","sequence":"first","affiliation":[{"name":"Division of Translational Informatics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwanoha, Kashiwa, Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Watanabe","sequence":"first","affiliation":[{"name":"School of Pharmacy, Shujitsu University, Nishigawara, Okayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Kinoshita","sequence":"first","affiliation":[{"name":"Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Asahimachi, Abeno-ku, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riu","family":"Yamashita","sequence":"first","affiliation":[{"name":"Division of Translational Informatics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwanoha, Kashiwa, Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Haeno","sequence":"first","affiliation":[{"name":"Division of Translational Genomics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwanoha, Kashiwa, Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigekazu","family":"Takemura","sequence":"first","affiliation":[{"name":"Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Asahimachi, Abeno-ku, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shogo","family":"Tanaka","sequence":"first","affiliation":[{"name":"Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Asahimachi, Abeno-ku, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeru","family":"Marubashi","sequence":"first","affiliation":[{"name":"Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Nakamichi, Higashinari-ku, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukari","family":"Totsuka","sequence":"first","affiliation":[{"name":"Division of Carcinogenesis & Cancer Prevention, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuhiro","family":"Shibata","sequence":"first","affiliation":[{"name":"Division of Cancer Genomics, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Nakagama","sequence":"first","affiliation":[{"name":"National Cancer Center, Tsukiji, Chuo-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Ochiai","sequence":"first","affiliation":[{"name":"Pathology Division, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwanoha, Kashiwa, Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoji","family":"Nakamori","sequence":"first","affiliation":[{"name":"Department of Surgery, Osaka National Hospital, Hoenzaka, Chuo-ku, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoji","family":"Kubo","sequence":"first","affiliation":[{"name":"Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Asahimachi, Abeno-ku, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuya","family":"Tsuchihara","sequence":"first","affiliation":[{"name":"Division of Translational Informatics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwanoha, Kashiwa, Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,6,20]]},"reference":[{"key":"2020051404380407400_CIT0001","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1002\/jhbp.86","article-title":"Case series of 17 patients with cholangiocarcinoma among young adult workers of a printing company in Japan","volume":"21","author":"Kubo","year":"2014","journal-title":"J. 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