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Liquid biopsy sequencing for liver cancer and pancreatic tumor

Research Project

Project/Area Number 15H04814
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Nakagawa Hidewaki  国立研究開発法人理化学研究所, 統合生命医科学研究センター, チームリーダー (50361621)

Co-Investigator(Kenkyū-buntansha) 山上 裕機  和歌山県立医科大学, 医学部, 教授 (20191190)
Co-Investigator(Renkei-kenkyūsha) Kawakami Yoshiiku  広島大学, 医学部, 講師 (70403516)
Fujimoto Akihiro  国立研究開発法人理化学研究所, 統合生命医科学研究センター, 副チームリーダー (30525853)
Wardell Chris  国立研究開発法人理化学研究所, 統合生命医科学研究センター, 研究員 (70748805)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2017: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2016: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2015: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
KeywordsLiquid biopsy / シークエンス / 肝臓がん / 膵臓がん / IPMT / 膵液 / がんゲノム / cfDNA / 膵腫瘍 / liquid biopsy / 膵がん / 癌 / ゲノム / 病理学 / ゲノム診断 / がん
Outline of Final Research Achievements

Exome sequencing of the cfDNAs (cell-free DNAs) in pancreatic juices from 37 IPMT patients and a half of samples were found to have KRAS or GNAS mutations and some had mutations of TP53 and RNF43. Loss of 17p13 and amplification of 8q24 were found in the pancreatic juice cfDNAs. We identified some genomic markers in pancreatic juices associated with histological grade of IPMT. We also deeply sequenced 100 liver cancer genes of plasma cfDNA from seven liver cancer patients after constructing new NGS libraries installed with molecular barcoding system. We improved the algorism to obtain the consensus reads and read filtering from these data, and succeed in calling somatic variants with more than 1% of VAF (variant allele frequency) in cfDNA. But less than 1% VAF is still difficult to discriminate from PCR and sequencing errors.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (12 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (2 results) Journal Article (6 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (4 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results)

  • [Int'l Joint Research] ヴェローナ大学(イタリア)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] ブロード研究所/ハーバード大学+MIT(米国)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Genomic Characterization of Biliary Tract Cancers Identifies Driver Genes and Predisposing Mutations2018

    • Author(s)
      Wardell CP, Fujita M, Yamada T, Simbolo M, Fassan M, Karlic R, Polak P, Kim J, Hatanaka Y, Maejima K, Lawlor RT, Nakanishi Y, Mitsuhashi T et al
    • Journal Title

      J Hepatol

      Volume: - Issue: 5 Pages: 959-969

    • DOI

      10.1016/j.jhep.2018.01.009

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Whole genome sequencing discriminates hepatocellular carcinoma with intrahepatic metastasis from multi-centric tumors2017

    • Author(s)
      Furuta M, Ueno M, Fujimoto A, Hayami S, Yasukawa S, Kojima F, Arihiro K, Kawakami Y, Wardell CP, Shiraishi Y, Tanaka H, Nakano K, Maejima K, Sasaki-Oku A, Tokunaga N, Boroevich KA, Abe T, Aikata H, Ohdan H, Gotoh K, Kubo M, Tsunoda T, Miyano S, Chayama K, Yamaue H, Nakagawa H
    • Journal Title

      J Hepatol

      Volume: 66(2) Issue: 2 Pages: 363-373

    • DOI

      10.1016/j.jhep.2016.09.021

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] がん診断の新たなマテリアルcfDNA2016

    • Author(s)
      西塚哲、谷上賢瑞、八谷剛史、中川英刀
    • Journal Title

      実験医学

      Volume: 34 Pages: 948-952

    • Related Report
      2016 Annual Research Report
  • [Journal Article] 臨床現場からのctDNAサンプル抽出まで2016

    • Author(s)
      西塚哲、谷上賢瑞、八谷剛史、中川英刀
    • Journal Title

      実験医学

      Volume: 34 Pages: 1319-1324

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Whole genome mutational landscape and characterization of non-coding and structural mutations in liver cancer.2016

    • Author(s)
      Fujimoto A et al.
    • Journal Title

      Nat Genet

      Volume: 48 Issue: 5 Pages: 500-509

    • DOI

      10.1038/ng.3547

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Circulating tumor DNA analysis for liver cancers and its usefulness as a liquid biopsy.2015

    • Author(s)
      Ono A, Fujimoto A, Yamamoto Y, Akamatsu S, Nobuhiko H, Imamura M, Kawaoka T, Tsuge M, Abe H, Hayes CN, Miki D, Furuta M, Tsunoda T, Miyano S, Kubo M, Aikata H, Ochi H, Kawakami Y, Arihiro K, Ohdan H, Nakagawa H, Chayama K
    • Journal Title

      Cellular and Molecular Gastroenterology and Hepatology

      Volume: 1 Issue: 5 Pages: 516-534

    • DOI

      10.1016/j.jcmgh.2015.06.009

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Cell-free DNAのシークエンス解析の課題2017

    • Author(s)
      中川 英刀
    • Organizer
      NGS現場の会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Cell-free DNA analysis for liver cancer and pancreatic cancer as a liquid biopsy for precision monitoring and diagnosis2016

    • Author(s)
      Hidewaki Nakagawa
    • Organizer
      AGBT Precison Medicine
    • Place of Presentation
      Phoenix, USA
    • Year and Date
      2016-09-23
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Sequencing analysis of plasma and pancreatic juice cell-free DNAs for cancer diagnosis2016

    • Author(s)
      中川 英刀
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜 (神奈川県、横浜)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Cancer genome profiling by NGS of archives and liquid biopsy samples2015

    • Author(s)
      中川 英刀
    • Organizer
      日本がん学会総会
    • Place of Presentation
      名古屋国際会議場(名古屋)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited

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Published: 2015-04-16   Modified: 2019-03-29  

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