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Usefulness of multigene liquid biopsy of bile for identifying driver genes of biliary duct cancers.

Author information

Affiliations

  • 1. Division of Molecular and Cellular Oncology, Miyagi Cancer Center Research Institute, Natori, Japan.
      Authors
    • Ito S 1
    • Soma S 1
    • Yasuda J 1
    (3 authors)
  • 2. Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
      Authors
    • Ando M 2
    • Aoki S 2
    • Zhang J 2
    • Hirano N 2
    • Kashiwagi R 2
    • Yoshimachi S 2
    • Sato H 2
    • Kusaka A 2
    • Iseki M 2
    • Inoue K 2
    • Mizuma M 2
    • Nakagawa K 2
    • Unno M 2
    (13 authors)
  • 3. Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
      Authors
    • Murakami K 3
    (1 author)
  • 4. Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
      Authors
    • Kume K 4
    • Masamune A 4
    (2 authors)
  • 5. Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, Natori, Japan.
      Authors
    • Asano N 5
    (1 author)

ORCIDs linked to this article

Cancer Science, 08 Oct 2024,
https://doi.org/10.1111/cas.16365 PMID: 39377143 

Abstract 

Liquid biopsy (LB) is an essential tool for obtaining tumor-derived materials with minimum invasion. 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-free 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-derived 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.

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Read article at publisher's site: https://doi.org/10.1111/cas.16365

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Funding 

Funders who supported this work.

Japan Society for the Promotion of Science (5)