Novel treatment of biliary tract cancer by targeting genomic diversity using Bile cell-free DNA

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08748
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Tohoku University
• Principal Investigator: Nakagawa Kei 東北大学, 医学系研究科, 准教授 (20542294)
• Co-Investigator(Kenkyū-buntansha): 青木 修一 東北大学, 大学病院, 助教 (30844451)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 胆道癌 / ゲノムプロファイリング / 予後予測因子 / プレシジョンメデジン

Outline of Final Research Achievements

The aim of this study is to evaluate the quality of cf-DNA in bile as a liquid sample and to identify the possibility of obtaining genomic profiling for personalized therapy. Thirteen cases undergoing surgical resection in pancreatic biliary tract cancer with bile duct invasion were collected. DNA was extracted from the resected specimens and whole exome sequencing revealed pathological mutations in TP53, ABCA8, BRCA2, FGFR2, APC, SMAD4 and NRAS. cf-DNA was extracted from bile samples from 13 cases and plasma samples from 9 cases. The results showed that bile contained more cf-DNA and had longer DNA fragments than plasma. Furthermore, the most representative gene mutations, such as TP53, KRAS, NRAS, and SMAD4, could be detected in bile cf-DNA. In conclusion, bile cf-DNA has the quality and quantity suitable for genetic analysis and reflects tumor-derived genetic mutations. Bile cf-DNA was considered a useful tool as a liquid biopsy for detecting genomic profiling.

Free Research Field

肝胆膵癌の診断と集学的治療

Academic Significance and Societal Importance of the Research Achievements

癌診断で入手可能なサンプルで、血液より感度高く遺伝子検索が可能であった。今後の予後予測因子や治療適応の可能性が広がった。サンプルの保管方法や処理について実績から提案が可能になった。
今後汎用性のあるパネルシークエンスのためにターゲットを絞って検索する必要性が考えられた。カットオフや胆道癌の中での部位別の違いについて今後検証の課題を提案できた。