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Cancer fluid biopsy for childhood malignancies using cell-free nucleotides

Research Project

Project/Area Number 17H05102
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Pediatric surgery
Research InstitutionHiroshima University

Principal Investigator

Ueda Yuka  広島大学, 病院(医), 講師 (70624641)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥25,350,000 (Direct Cost: ¥19,500,000、Indirect Cost: ¥5,850,000)
Fiscal Year 2019: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Fiscal Year 2018: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Fiscal Year 2017: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
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 / 小児腫瘍学 / 診断 / 一細胞解析
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.

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。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (25 results)

All 2019 2018 2017

All Journal Article (4 results) (of which Peer Reviewed: 1 results) Presentation (21 results) (of which Int'l Joint Research: 6 results)

  • [Journal Article] Gene expression profiling in hepatoblastoma cases of the Japanese Study Group for Pediatric Liver Tumors-2 (JPLT-2) trial2019

    • Author(s)
      Hiyama E, Ueda Y, Kurihara S, Kawashima K, Ikeda K, Morihara N, Fukazawa T, Kanawa M,
    • Journal Title

      European Journal of Molecular Cancer

      Volume: 1 Pages: 2-8

    • DOI

      10.31487/j.ejmc.2018.01.003

    • Related Report
      2019 Annual Research Report
  • [Journal Article] 術後3年5ヶ月で再手術を要した巨大水腎症の1例 遅発性再発の要因についての一考察2018

    • Author(s)
      Tanaka M, Kohashi K, Kushitani K, Yoshida M, Kurihara S, Kawashima M, Ueda Y, Souzaki R,
    • Journal Title

      日本小児泌尿器科学会雑誌

      Volume: 27 Pages: 62-87

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 「Inflammatory myofibroblastic tumors of the lung carrying a chimeric A2M-ALK gene: report of two infantile cases and review of the differential diagnosis of inpantile pulmonary lesions」2017

    • Author(s)
      Tanaka M, Kohashi K, Kushitani K, Yoshida M, Kurihara S, Kawashima M, Ueda Y, Souzaki R, Kinoshita Y, Oda Y, Takeshima Y, Hiyama E, Taguchi T, Tanaka Y.
    • Journal Title

      Human Pathology

      Volume: 66 Pages: 177-182

    • Related Report
      2017 Annual Research Report
  • [Journal Article] 「Inflammatory myofibroblastic tumors of the lung carrying a chimeric A2M-ALK gene: report of 2 infantile cases and review of the differential diagnosis of infantile pulmonary lesions」2017

    • Author(s)
      Tanaka M, Kohashi K, Kushitani K, Yoshida M, Kurihara S, Kawashima M, Ueda Y, Souzaki R, Kinoshita Y, Oda Y, Takeshima Y, Hiyama E, Taguchi T, Tanaka Y
    • Journal Title

      Human Pathology

      Volume: 66 Pages: 177-182

    • Related Report
      2017 Annual Research Report
  • [Presentation] Circulating Tumor Cells and tumor DNA in Liquid Biopsy for childhood malignancy2019

    • Author(s)
      Hiyama E. Ueda Y, Kurihara S, Hiyama K
    • Organizer
      PAPS 52nd Annual Meeting 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 当院のマススクリーニング終了後の神経芽腫群症例の検討2019

    • Author(s)
      栗原 將、檜山 英三、上田 祐華
    • Organizer
      第60回中国四国小児がん研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Late toxicities, especially second malignancies, with GWAS analysis in hepatoblastoma cases treated in the Japanese Study Group for Pediatric Liver Tumor protocol-22019

    • Author(s)
      Hiyama E, Kurihara S, Ueda Y, Hishiki T, Ida K, Iehara T, Oue T, Yano M, Watanabe K, Hoshino K, Ko K, Tanaka Y
    • Organizer
      ASCO Annual Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 新生児腸重積症(回腸-回腸型)の一例2019

    • Author(s)
      栗原將、兒島正人、上田祐華、檜山英三
    • Organizer
      第58回日本小児外科学会中国四国地方会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 次世代シークエンサ―を用いた神経芽腫患者のマイクロRNAの検討2019

    • Author(s)
      Arfan Ahmad、檜山 洋子、木村 真吾、上田 祐華、栗原 將、山岡 絵美、檜山 英三
    • Organizer
      第57回日本癌治療学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 肝中央二区域切除を施行した肝芽腫の2 例Two Cases of central bisectionectomy of liver for hepatoblastoma2019

    • Author(s)
      栗原 將,上田 祐華,兒島 正人,唐川 修平,川口 浩史,檜山 英三
    • Organizer
      第61回日本小児血液・がん学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 当院で経験した18 トリソミーに発症した肝芽腫症例の検討Clinical investigation of hepatoblastoma cases with 18 trisomy2019

    • Author(s)
      上田 祐華,栗原 將,兒島 正人,谷口 真紀,下村 麻衣子,唐川 修平,川口 浩史,檜山 英三
    • Organizer
      第61回日本小児血液・がん学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 肝芽腫に対するβ カテニン遺伝子異常を用いたリキッドバイオプシーの開発Liquid biopsy using β-catenin aberrations in hepatoblastoma2019

    • Author(s)
      Masato Kojima, Sho Kurihara, Yuka Ueda, Eiso Hiyama
    • Organizer
      第61回日本小児血液・がん学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 家族性大腸腺腫症の家族歴をもつ、肝芽腫の2 例Two cases of hepatoblastoma with a parental history of familial adenomatous polyposis2019

    • Author(s)
      Maki Taniguchi, Shuhei Karakawa, Ayaka Suzawa, Kumi Chogahara, Ayaka Ohno, Maiko Shimomura, Sho Kurihara, Yuka Ueda, Eiso Hiyama, Hiroshi Kawaguchi
    • Organizer
      第61回日本小児血液・がん学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 腸重積症を発症し開腹手術を施行したPeutz-Jeghers 症候群の11歳男児の1例2019

    • Author(s)
      兒島正人,栗原 將,上田祐華,檜山英三
    • Organizer
      第56回日本小児外科学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 当院での小児縦隔腫瘍の初診時外科的介入についての検討2019

    • Author(s)
      栗原 將,上田祐華,兒島正人,檜山英三
    • Organizer
      第56回日本小児外科学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 初診時に呼吸循環障害が危惧された神経芽腫の8例.2018

    • Author(s)
      栗原 將, 檜山 英三, 上田 祐華
    • Organizer
      第59回中国四国小児がん研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 当院で最近経験した小児肺腫瘍性病変の3例。2018

    • Author(s)
      栗原 將, 檜山 英三, 上田 祐華、田中 祐吉
    • Organizer
      第55回日本小児外科学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 器質的疾患を認めず膀胱肉柱形成所見を認めた2症例.2018

    • Author(s)
      栗原 將, 上田 祐華, 檜山 英三
    • Organizer
      第57回日本小児外科学会中国四国地方会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 小児固形腫瘍初診時における外科的生検についての検討 (The examination about surgical biopsy for childhood solid tumors).2018

    • Author(s)
      栗原 將, 檜山 英三, 上田 祐華
    • Organizer
      第60回日本小児血液・がん学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] NABIGATION SURGERY USING ICG FLUORESCENCE IMAGING FOR HEPATOBLASTOMA LUNG METASECTOMY2017

    • Author(s)
      Hiyama E, Kurihara S, Ueda Y, Oue T, Kitagawa N, JCCG Liver Tumor Committee(JPLT), Japan
    • Organizer
      SIOPEL SPRING MEETING 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 巨大な後腹膜リンパ管腫に鼡径ヘルニアが合併し鼠径部に滑脱していた1例2017

    • Author(s)
      栗原 將,檜山 英三,河島 茉澄,上田 祐華
    • Organizer
      第54回日本小児外科学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] PHARMACOGENETICS ANALYSIS for TREATMENT-RELATED TOXICITIES OF HEPATOBLASTOMA PATIENTS IN JAPAN2017

    • Author(s)
      Hirahara S, Hiyama E, Kimura S,Kuriahra S, Kawashima M, Ueda Y, Onitake Y.
    • Organizer
      The 49th Congress of the International Society of Paediatric Oncology (SIOP2017)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Surgical and Interventional Treatment for ruptured hepatic Tumors in Japanese Study Group Experience2017

    • Author(s)
      Hiyama E, Hishiki T, Hoshino K, Yokoi A, Tamata T, Kazama T, Honda S, Taguchi T, Kurihara S, Kawashima M, Ueda Y
    • Organizer
      The 49th Congress of the International Society of Paediatric Oncology (SIOP2017)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Integrated Genetic and Epigenetic Analysis novel Molecular Subgroups in Hepatoblastoma2017

    • Author(s)
      Hiyama E, Kurihara S, hirano S, Irisuna F, Ueda Y, Kawashima M
    • Organizer
      The 49th Congress of the International Society of Paediatric Oncology (SIOP2017)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The probability of liquid biopsy as non-invasive diagnostic tool for childhood solid tumors(小児悪性固形患児における非侵襲的診断法としてのリキッドバイオプシーの可能性)2017

    • Author(s)
      Kurihara S, Hiyama E, Ueda Y
    • Organizer
      第59回日本小児血液・がん学会学術集会
    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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