Cancer fluid biopsy for childhood malignancies using cell-free nucleotides

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H05102
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Pediatric surgery
• Research Institution: Hiroshima University
• Principal Investigator: Ueda Yuka 広島大学, 病院(医), 講師 (70624641)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 小児がん / リキッドバイオプシー / 遊離DNA / マイクロRNA / 神経芽腫 / 肝芽腫 / 次世代シークエンサー / 遺伝子変化

Outline of Final Research Achievements

Tumor-specific genetic changes (mutation, deletion, translocation) and specific miRNA expression were analyzed by next-generation sequence analysis (NGS) using cell-free nucleic acids (cell-free DNA and microRNA) derived from plasma samples of approximately 200 children with solid malignant tumors. These patients were treated in Hiroshima University Hospital and whose tumor and plasma samples were simultaneously stored. As genetic alterations, MYCN amplification and ALK mutations in neuroblastoma, and CTNNB1 abnormalities in hepatoblastoma were detected. In neuroblastoma, three miRNAs associated with malignancy (miR-375, miR-92a-3p and miR-99a-5p) were also identified. From these results, it was considered that the NGS analysis method using cell-free nucleic acid and miRNA could be available for a bedside cancer fluid biopsy method that is highly reliable and minimally invasive in children.

Free Research Field

小児外科

Academic Significance and Societal Importance of the Research Achievements

小児固形がんは、100を超える様々な腫瘍があり、小円形細胞が多く病理診断に加えて分子診断による確実な診断の基に的確な治療を行うことが必須で、通常は外科的に生検を施行する。小児に対する腫瘍生検は全身麻酔が必要でさらに、部位により必ずしも容易でない。本研究にて、体液特に血液中の腫瘍由来の遊離核酸とエクソソームを用いた次世代シークエンサーによる低侵襲で迅速かつ正確な小児Cancer Liquid Biopsyの確立が可能となると考えられ、今後、分子標的による個別化療法の選択、治療効果判定や再発モニタリングへの展開が期待される。