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Revealing cancer-cell evolution and intra-tumor heterogeneity by single-cell genome and transcriptome analysis

Research Project

Project/Area Number 15K06916
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Medical genome science
Research InstitutionNational Cancer Center Japan

Principal Investigator

Kato Mamoru  国立研究開発法人国立がん研究センター, 研究所, 部門長 (40391916)

Co-Investigator(Kenkyū-buntansha) 筆宝 義隆  国立研究開発法人国立がん研究センター, 研究所, 客員研究員 (30359632)
新井 康仁  国立研究開発法人国立がん研究センター, 研究所, 主任研究員 (80222727)
Co-Investigator(Renkei-kenkyūsha) SHIBATA Tatsuhiro  国立がん研究センター, がんゲノミクス分野, 分野長 (90311414)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsがんゲノム / 一細胞シークエンス / 腫瘍内多様性 / 腫瘍内不均質性 / がん細胞進化 / バイオインフォマティクス / がん不均質性
Outline of Final Research Achievements

To reveal heterogeneity dynamics of caner, we sampled single cells in a colorectal cancer mouse model right before, and 1 and 3 months after transplantation, and then used C1 to sequence both single-cell exome and transcriptome. We revealed that the heterogeneity of DNA decreased after transplantation, whereas that of RNA increased. This heterogeneity increase corresponded to the newly generated subpopulations of cancer cells. They had distinct features in markers such as cell proliferation, epithelial-mesenchymal transformation, and stem cell, and we revealed the dynamics of the feature change. We also found associations with metastatic colonization and a certain clinical factor.

Report

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

    (26 results)

All 2018 2017 2016 2015 Other

All Journal Article (13 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 12 results,  Open Access: 4 results,  Acknowledgement Compliant: 6 results) Presentation (11 results) (of which Invited: 2 results) Remarks (2 results)

  • [Journal Article] Epigenetic landscape influences the liver cancer genome architecture.2018

    • Author(s)
      Hama N, Totoki Y, Miura F, Tatsuno K, Saito-Adachi M, Nakamura H, Arai Y, Hosoda F, Urushidate T, Ohashi S, Mukai W, Hiraoka N, Aburatani H, Ito T, Shibata T.
    • Journal Title

      Nat Commun.

      Volume: 9

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] SET/PP2A/E2F1 Axis Enhances Gastric Cancer Cell Stemness2018

    • Author(s)
      Enjoji S, Yabe R, Tsuji S, Yoshimura K, Kawasaki H, Sakurai M, Sakai Y, Takenouchi H, Yoshino S, Hazama S, Nagano H, Oshima H, Oshima M, Vitek M, Matsuura T, Hippo Y, Usui T, Ohama T, and Sato K.
    • Journal Title

      Mol. Cancer. Res

      Volume: 16 Pages: 554-563

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sweepstake evolution revealed by population-genetic analysis of copy-number alterations in single genomes of breast cancer2017

    • Author(s)
      Mamoru Kato, Daniel A. Vasco, Ryuichi Sugino, Daichi Narushima, and Alexander Krasnitz
    • Journal Title

      Royal Society Open Science

      Volume: 4

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ex vivo model of non-small cell lung cancer using mouse lung epithelial cells.2017

    • Author(s)
      Sato T, Morita M, Tanaka R, Inoue Y, Nomura M, Sakamoto Y, Miura K, Ito S, Sato I, Tanaka N, Abe, Takahashi S, Kawai M, Sato M, Hippo Y, Shima H, Okada Y and Tanuma N.
    • Journal Title

      Oncology Lett.

      Volume: 14 Pages: 6863-6868

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genomic and transcriptomic analysis of imatinib resistance in gastrointestinal stromal tumors2017

    • Author(s)
      Tsuyoshi Takahashi, Asmaa Elzawahry, Sachiyo Mimaki, Eisaku Furukawa, Rie Nakatsuka, Hiromi Nakamura, Takahiko Nishigaki, Satoshi Serada, Tetsuji Naka, Seiichi Hirota, Tatsuhiro Shibata, Katsuya Tsuchihara, Toshirou Nishida, and Mamoru Kato
    • Journal Title

      Genes, Chromosomes & Cancer

      Volume: 56 Pages: 303-313

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Mismatch repair deficiency commonly precedes adenoma formation in Lynch syndrome-associated colorectal tumorigenesis2017

    • Author(s)
      Shigeki Sekine, Taisuke Mori, Reiko Ogawa, Masahiro Tanaka, Hiroshi Yoshida, Hirokazu Taniguchi, Takeshi Nakajima, Kokichi Sugano, Teruhiko Yoshida, Mamoru Kato, Eisaku Furukawa, Atsushi Ochiai, and Nobuyoshi Hiraoka
    • Journal Title

      Modern Pathology

      Volume: 印刷中

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] The induction of selected Wnt target genes by Tcf1 mediates generation of tumorigenic colon stem cells2017

    • Author(s)
      Daisuke Shiokawa, Hirokazu Ohata, Ai Sato, Michihiro Muto, Shigeki Sekine, Masahito Hosokawa, Mamoru Kato, Hideki Kanbara, Tatsuhiro Shibata, Koji Okamoto
    • Journal Title

      Cell Reports

      Volume: 19 Pages: 981-994

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] NUTM2A-CIC fusion small round cell sarcoma: A genetically distinct variant of CIC-rearranged sarcoma Human Pathology2017

    • Author(s)
      Sugita S, Arai Y, Aoyama T, Asanuma H, Mukai W, Hama N, Emori M, Shibata T, Hasegawa T.
    • Journal Title

      Human Pathology

      Volume: 印刷中

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Identification of novel mutations in Japanese ovarian clear cell carcinoma patients using optimized targeted NGS for clinical diagnosis2017

    • Author(s)
      Maru Y, Tanaka N, Ohira M, Itami M, Hippo Y, Nagase H
    • Journal Title

      Gynecol Oncol

      Volume: 144 Pages: 377-383

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Integrated multiregional analysis proposing a new model of colorectal cancer evolution2016

    • Author(s)
      Ryutaro Uchi, ..., Mamoru Kato, ..., Koshi Mimori
    • Journal Title

      PLOS Genetics

      Volume: 12 Pages: 1-24

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genomic sequencing identifies ELF3 as a driver of ampullary carcinoma2016

    • Author(s)
      Shinichi Yachida, ..., Mamoru Kato, ..., Tatsuhiro Shibata
    • Journal Title

      Cancer Cell

      Volume: 29 Pages: 229-240

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Lentivirus-based stable gene delivery into intestinal organoids2016

    • Author(s)
      Maru Y, Orihashi K, Hippo Y
    • Journal Title

      Methods Mol Biol

      Volume: 1422 Pages: 13-21

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 一細胞シークエンスのデータ解析2016

    • Author(s)
      加藤 護
    • Journal Title

      医学のあゆみ

      Volume: 258 Pages: 317-323

    • Related Report
      2016 Research-status Report
    • Acknowledgement Compliant
  • [Presentation] Single-cell sequencing combined with mathematical approaches reveals the generative processes of intra-tumor heterogeneity2017

    • Author(s)
      Mamoru Kato
    • Organizer
      NGS Field Meeting
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] オルガノイド移植モデルおよびPDXによる胆道・膵管発がん再構成2017

    • Author(s)
      筆宝 義隆
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 3次元オルガノイド培養のがん研究への応用2017

    • Author(s)
      筆宝 義隆
    • Organizer
      第26回日本癌病態治療研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] オルガノイドを用いた発がん過程のin vitro再構成2017

    • Author(s)
      筆宝 義隆
    • Organizer
      第58回日本臨床細胞学会総会春季大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Single-cell sequencing reveals genomic and transcriptomic dynamics during tumor development in a mouse model2016

    • Author(s)
      加藤 護
    • 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・横浜市)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] Oncogenic driver fusion genes in biliary tract cancer2016

    • Author(s)
      新井康仁、中村浩実、十時 泰、濱 奈津子、尾島英知、細田文恵、島田和明、森実千種、奥坂拓志、柴田龍弘
    • 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・横浜市)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] オルガノイドを用いた胆嚢発がんモデルの確立2016

    • Author(s)
      筆宝義隆、丸喜明、落合雅子、松浦哲也、今井俊夫
    • 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・横浜市)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] in vitroモデルが明らかにするマウス膵管発がんにおけるKras遺伝子材の重要性2016

    • Author(s)
      松浦哲也、落合雅子、中島淳、今井俊夫、筆宝義隆
    • 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・横浜市)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] レンチウイルスを用いたマウス胃細胞からの発がん誘導2016

    • Author(s)
      丸 喜明、松浦 哲也、落合 雅子、筆宝 義隆
    • Organizer
      第20回日本がん分子標的治療学会学術集会
    • Place of Presentation
      別府国際コンベンションセンター(大分県・別府市)
    • Year and Date
      2016-05-30
    • Related Report
      2016 Research-status Report
  • [Presentation] Tumor heterogeneity and single-cell sequencing2015

    • Author(s)
      Mamoru Kato
    • Organizer
      74rd Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      Nagoya, Japan
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] Bioinformatics for clinical sequencing and single-cell sequencing2015

    • Author(s)
      Mamoru Kato
    • Organizer
      Mathematics in Cancer Genome Analysis, Mathematical Cooperation Program 2015
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      2015-09-30
    • Related Report
      2015 Research-status Report
  • [Remarks] 一細胞シークエンスと数理解析による、腫瘍内不均質性とがん細胞進化の解明

    • URL

      https://www.ncc.go.jp/jp/ri/department/bioinformatics/project/020/index.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] 一細胞シークエンスによる、腫瘍内不均質性とがん細胞進化の解明

    • URL

      http://www.nccri.ncc.go.jp/s031/010/020/20151208182431.html

    • Related Report
      2016 Research-status Report 2015 Research-status Report

URL: 

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

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