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Bile has been shown to contain much higher free nucleic acid levels than blood plasma and can be collected through endoscopic procedures. Therefore, bile possesses high potential as a source of tumor derived cell\u2010free DNA (cfDNA) for bile duct cancers. In this study, we show that a multigene panel for plasma LB can also be applied to bile cfDNA for comparing driver gene mutation detection in other sources (plasma and tumor tissues of the corresponding patients). We collected cfDNA samples from the bile of 24 biliary tract cancer cases. These included 17 cholangiocarcinomas, three ampullary carcinoma, two pancreatic cancers, one intraductal papillary mucinous carcinoma, and one insulinoma. Seventeen plasma samples were obtained from the corresponding patients before surgical resection and subjected to the LiquidPlex multigene panel LB system. We applied a machine learning approach to classify possible tumor\u2010derived variants among the prefiltered variant calls by a LiquidPlex analytical package with high fidelity. Among the 17 cholangiocarcinomas, we could detect cancer driver mutations in the bile of 10 cases using the LiquidPlex system. Of the biliary tract cancer cases examined with this method, 13 (54%) and 4 (17%) resulted in positive cancer driver mutation detection in the bile and plasma cfDNAs, respectively. These results suggest that bile is a more reliable source for LB than plasma for multigene panel analyses of biliary tract cancers.<\/jats:p>","DOI":"10.1111\/cas.16365","type":"journal-article","created":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T09:07:39Z","timestamp":1728378459000},"page":"4054-4063","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Usefulness of multigene liquid biopsy of bile for identifying driver genes of biliary duct cancers"],"prefix":"10.1111","volume":"115","author":[{"given":"Shin","family":"Ito","sequence":"first","affiliation":[{"name":"Division of Molecular and Cellular Oncology Miyagi Cancer Center Research Institute  Natori Japan"},{"name":"Division of Cancer Molecular Biology Tohoku University Graduate School of Medicine  Sendai 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