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Modeling fusion gene-associated bone and soft tissue sarcoma and its application to therapies

Research Project

Project/Area Number 26250029
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Tumor biology
Research InstitutionJapanese Foundation for Cancer Research

Principal Investigator

Nakamura Takuro  公益財団法人がん研究会, がん研究所 発がん研究部, 部長 (00180373)

Co-Investigator(Kenkyū-buntansha) 森 誠一  公益財団法人がん研究会, その他部局等, 研究員 (10334814)
黒田 雅彦  東京医科大学, 医学部, 教授 (80251304)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥39,910,000 (Direct Cost: ¥30,700,000、Indirect Cost: ¥9,210,000)
Fiscal Year 2016: ¥13,000,000 (Direct Cost: ¥10,000,000、Indirect Cost: ¥3,000,000)
Fiscal Year 2015: ¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000)
Fiscal Year 2014: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000)
Keywords発がん / 融合遺伝子 / 骨軟部肉腫 / 動物モデル / 発生母地 / 転移 / 微小環境 / 協調遺伝子 / 胞巣状軟部肉腫 / CIC-DUX4肉腫 / 滑膜肉腫 / Ewing肉腫 / 治療評価 / CIC-DUX4 / 転移機構
Outline of Final Research Achievements

It has been challenging to create fusion gene-associated bone and soft tissue sarcoma. We have generated mouse models for Ewing sarcoma, alveolar soft part sarcoma, CIC-DUX4 sarcoma and synovial sarcoma, and established the ex vivo model system of sarcoma. These four models recapitulate phenotypes of human sarcoma in morphology, gene expression and biological characteristics. Using the models, cell-of-origin of Ewing sarcoma, molecular mechanisms of hematogenous metastasis in alveolar soft part sarcoma, novel biomarkers for CIC-DUX4 sarcoma and cooperative genes of SYT-SSX1 in synovial sarcoma development have been clarified. Therapeutic effects of inhibitors and anti-cancer drugs were evaluated in vitro and in vivo using Ewing sarcoma and CIC-DUX4 sarcoma models.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (49 results)

All 2017 2016 2015 2014 Other

All Int'l Joint Research (6 results) Journal Article (17 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 17 results,  Open Access: 11 results,  Acknowledgement Compliant: 4 results) Presentation (20 results) (of which Int'l Joint Research: 5 results,  Invited: 19 results) Remarks (4 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Int'l Joint Research] Memorial Sloan Kettering Cancer Center/Georgetown University/University of California San Francisco(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] University of Glasgow(英国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] Georgetown University/Stanford University/Tulane University(米国)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] Curie Institute(フランス)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] Medical University of Vienna(オーストリア)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] University of Ulm(ドイツ)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Modeling alveolar soft part sarcoma unveils novel mechanisms of metastasis.2017

    • Author(s)
      Tanaka M, Homme M, Yamazaki Y, Shimizu R, Takazawa Y, Nakamura T
    • Journal Title

      Cancer Res

      Volume: 77 Issue: 4 Pages: 897-904

    • DOI

      10.1158/0008-5472.can-16-2486

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Takuro Nakamura CIC-DUX4 induces small round cell sarcomas distinct from Ewing sarcoma2017

    • Author(s)
      Yoshimoto T, Tanaka M, Homme M, Yamazaki Y, Takazawa Y, Antonescu CR, Nakamura T
    • Journal Title

      Cancer Res

      Volume: 印刷中 Issue: 11 Pages: 2927-2937

    • DOI

      10.1158/0008-5472.can-16-3351

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Transposon insertional mutagenesis in mice identifies human breast cancer susceptibility genes and signatures for stratification2017

    • Author(s)
      Chen L, Jenjaroenpun P, Pillai AM, Ivshina AV, Ow GS, Efthimios M, Zhiqun T, Tan TZ, Lee SC, Rogers K, Ward JM, Mori S, Adams DJ, Jenkins NA, Copeland NG, Ban KH, Kuznetsov VA, Thiery JP
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 114 Issue: 11

    • DOI

      10.1073/pnas.1701512114

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Serum miR-143 levels predict the pathological response to neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer2017

    • Author(s)
      Hiyoshi Y, Akiyoshi T, Inoue R, Murofushi K, Yamamoto N, Fukunaga Y, Ueno M, Baba H, Mori S, Yamaguchi T
    • Journal Title

      Oncotarget

      Volume: 印刷中 Issue: 45 Pages: 79201-79211

    • DOI

      10.18632/oncotarget.16760

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Combined experience of six independent laboratories attempting to create an Ewing sarcoma mouse model2016

    • Author(s)
      Minas TZ, Surdez D, Tahereh J, Tanak M, Howarth M, Kang HJ, Han J, Han ZY, Sax B, Kream BE, Hong SH, Tirode F, Tuckermann J, Toretsky JA, Kenner L, Kovar H, Lee S, Sweet-Cordero A, Nakamura T, Moriggi R, Delattre O, Uren A
    • Journal Title

      Oncotarget

      Volume: May 15 Issue: 21 Pages: 9388-9388

    • DOI

      10.18632/oncotarget.9388

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Co-operative leukemogenesis in acute myeloid leukemia and acute promyelocytic leukemia reveals C/EBPα as a common target of TRIB1 and PML/RARA2016

    • Author(s)
      Keeshan K, Vieugue P, Chaudhury S, Rishi L, Gaillard C, Liang L, Garcia E, Nakamura T, Omidvar N, Kogan SC
    • Journal Title

      Haematologica

      Volume: 101 Issue: 10 Pages: 1228-1236

    • DOI

      10.3324/haematol.2015.138503

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] STAT5A modulates chemokine receptor CCR6 expression and enhances pre‐B cell growth in a CCL20‐dependent manner2016

    • Author(s)
      Tsuruyama T, Hiratsuka T, Aini W, Nakamura T
    • Journal Title

      J Cell Biochem

      Volume: 117 Issue: 11 Pages: 2630-2642

    • DOI

      10.1002/jcb.25558

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of novel small hairpin RNAs that do not require processing by dicer or AGO22016

    • Author(s)
      Ohno S, Itano K, Harada Y, Asada K, Oikawa K, Kashiwazako M, Okuyama H, Kumagai K, Takanashi M, Sudo K, Ikeda N, Kuroda M.
    • Journal Title

      Mol Ther

      Volume: 24 Issue: 7 Pages: 1278-1289

    • DOI

      10.1038/mt.2016.81

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Topical Use of Angiopoietin-like Protein 2 RNAi-loaded Lipid Nanoparticles Suppresses Corneal Neovascularization.2016

    • Author(s)
      Taketani Y, Usui T, Toyono T, Shima N, Yokoo S, Kimakura M, Yamagami S, Ohno S, Onodera R, Tahara K, Takeuchi H, Kuroda M.
    • Journal Title

      Mol Ther Nucleic Acids.

      Volume: 5 Pages: e292-e292

    • DOI

      10.1038/mtna.2016.1

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ZFP521 contributes to pre-B-cell lymphoma genesis through modulation of the pre-B-cell receptor signaling pathway2016

    • Author(s)
      Hiratsuka T, Takei Y, Ohmori R, Imai Y, Ozeki M, Tamaki K, Nakamura T, Tsuruyama T
    • Journal Title

      Oncogene

      Volume: in press Issue: 25 Pages: 3227-3238

    • DOI

      10.1038/onc.2015.385

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MEIS1-mediated transactivation of synaptotagmin-like 1 promotes CXCL12/CXCR4 signaling and leukemogenesis.2016

    • Author(s)
      Yokoyama T, Nakatake M, Kuwata T, Couiznet A, Goitsuka R, Tsutsumi S, Aburatani H, Valk PJ, Delwel R, Nakamura T.
    • Journal Title

      J Clin Invest.

      Volume: 印刷中 Issue: 5 Pages: 1664-1678

    • DOI

      10.1172/jci81516

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The role of Trib1 in myeloid leukaemogenesis and differentiation2015

    • Author(s)
      Nakamura T
    • Journal Title

      Biochem Soc Trans

      Volume: 43 Issue: 5 Pages: 1104-1107

    • DOI

      10.1042/bst20150110

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Loss of homeodomain transcription factor Prep1 perturbs adult hematopoiesis in the bone marrow2015

    • Author(s)
      Yoshioka K, Oda A, Notsu C, Ohtsuka T, Kawai Y, Suzuki S, Nakamura T, Mabuchi Y, Matsuzaki Y, Goitsuka R
    • Journal Title

      PLoS One

      Volume: 5 Pages: 7826-7826

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Somatic chromosomal translocation between Ewsr1 and Fli1 loci leads to dilated cardiomyopathy in a mouse model.2015

    • Author(s)
      Tanaka M, Yamaguchi S, Yamazaki Y, Kinoshita H, Kuwahara K, Nakao K, Jay PY, Noda T, Nakamura T.
    • Journal Title

      Science Report

      Volume: 5 Issue: 1 Pages: 7826-7826

    • DOI

      10.1038/srep07826

    • NAID

      120007100130

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ewing’s sarcoma precursors are highly enriched in embryonic osteochondrogenic progenitors.2014

    • Author(s)
      Tanaka M, Yamazaki Y, Kanno Y, Igarashi K, Aisaki K, Kanno J, Nakamura T.
    • Journal Title

      J Clin Invest

      Volume: 121 Pages: 3061-3074

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Meis1 regulates epidermal stem cells and is required for skin tumorigenesis2014

    • Author(s)
      Okumura K, Saito M, Isogai E, Aoto Y, Hachiya T, Sakakibara Y, Katsuragi Y, Hirose S, Kominami R, Goitsuka R, Nakamura T and Wakabayashi Y.
    • Journal Title

      PLOS ONE

      Volume: 9 Issue: 7 Pages: e102111-e102111

    • DOI

      10.1371/journal.pone.0102111

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gene expression response to EWS-FLI1 in mouse embryonic cartilage.2014

    • Author(s)
      Tanaka M, Aisaki K, Kitajima S, Igarashi K, Kanno J, Nakamura T.
    • Journal Title

      Genomics Data

      Volume: 2 Pages: 296-298

    • DOI

      10.1016/j.gdata.2014.09.003

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 骨軟部肉腫の発症と転移機構の研究2017

    • Author(s)
      中村卓郎
    • Organizer
      金沢大学がん制御研究所共同利用・共同研究拠点シンポジウム
    • Place of Presentation
      金沢
    • Year and Date
      2017-02-14
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 肉腫における微小環境 マウスモデルを用いた解析2016

    • Author(s)
      中村卓郎
    • Organizer
      第1回日本肉腫学会年次総会
    • Place of Presentation
      京都
    • Year and Date
      2016-12-01
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Ewing肉腫の発生と悪性化におけるETS融合遺伝子の役割2016

    • Author(s)
      中村卓郎
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] A novel synovial sarcoma mouse model identifies cooperative genetic pathways with SS18-SSX12016

    • Author(s)
      Tanaka M, Nakamura T
    • Organizer
      Connective Tissue Oncology Society 2016 Annual Meeting
    • Place of Presentation
      Lisbon
    • Year and Date
      2016-11-09
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Studying novel aspects of cancer metastatic mechanisms using mouse models for sarcoma2016

    • Author(s)
      中村卓郎
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] がんのモデルマウス 動物個体を使った研究の面白さと将来性2016

    • Author(s)
      中村卓郎
    • Organizer
      先端モデル動物支援プラットフォーム若手技術講習会
    • Place of Presentation
      茅野
    • Year and Date
      2016-09-18
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Signaling and transcriptional network in myeloid leukemogenesis2016

    • Author(s)
      Nakamura T
    • Organizer
      The 5th JCA-AACR Special Joint Conference
    • Place of Presentation
      浦安
    • Year and Date
      2016-07-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 融合遺伝子発現とマウスモデルが明らかにする肉腫の発生進展機構2016

    • Author(s)
      中村卓郎
    • Organizer
      第105回日本病理学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2016-05-12
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Modeling Ewing's sarcoma and fusion gene-associated sarcoma: Tools to investigate cell-of-origin, metastatic mechanisms and genetic pathwaysodeling Ewing's sarcoma and fusion gene-associated sarcoma: Tools to investigate cell-of-origin, metastatic mechanisms and genetic pathways2015

    • Author(s)
      中村卓郎
    • Organizer
      日本肉腫学会記念シンポジウム
    • Place of Presentation
      京都
    • Year and Date
      2015-12-03
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Mouse models for fusion gene-associated sarcoma: a comprehensive approach2015

    • Author(s)
      Nakamura T
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] マウスモデルを用いた肉腫転移機構の解析2015

    • Author(s)
      中村卓郎
    • Organizer
      in vivoイメージングフォーラム2015
    • Place of Presentation
      東京
    • Year and Date
      2015-09-17
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Osteochondrogenic progenitors of mouse embryo as Ewing sarcoma cell-of-origin2015

    • Author(s)
      Nakamura T
    • Organizer
      ASSET-ENCCA Ewing Meeting
    • Place of Presentation
      Paris, France
    • Year and Date
      2015-05-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] The role of Trib1 in myeloid leukemogenesis and differentiation2015

    • Author(s)
      Nakamura T
    • Organizer
      Tribbles pseudokinases at the crossroads of metabolism, cancer, immunity and development
    • Place of Presentation
      Budapest, Hungary
    • Year and Date
      2015-04-22
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Molecular dissection of leukemic cell expansion in vivo2015

    • Author(s)
      Nakamura T
    • Organizer
      SNUCRI Cancer Symposium
    • Place of Presentation
      Hwasun Kumho Resort, Korea
    • Year and Date
      2015-04-01
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Histogenesis of Ewing's sarcoma2014

    • Author(s)
      Nakamura T
    • Organizer
      The Japan-United States International Workshop on the Sarcoma Research and Therapy
    • Place of Presentation
      Honolulu, Hawaii, U.S.A.
    • Year and Date
      2014-12-04
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Modeling fusion gene-associated bone and soft tissue sarcoma.2014

    • Author(s)
      Nakamura T
    • Organizer
      The 4th Japan-France Cancer Workshop
    • Place of Presentation
      京都
    • Year and Date
      2014-11-19
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] miR214 cooperates with SYT-SSX1 in malignant progression of synovial sarcoma2014

    • Author(s)
      Tanaka M, Nakamura T
    • Organizer
      第73回日本癌学会学術総会腫瘍別シンポジウム
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-27
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Modeling the cancer gene network and disease progression in vivo2014

    • Author(s)
      Nakamura T
    • Organizer
      第73回日本癌学会学術総会JCA-AACR Joint Symposium
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] The role of Sytl1, a downstream target gene of Meis1, in myeloid leukemogenesis2014

    • Author(s)
      Nakamura T
    • Organizer
      Tenth Annual Myeloid Meeting
    • Place of Presentation
      Cincinnati, Ohio, U.S.A.
    • Year and Date
      2014-05-05
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Modeling fusion gene-related bone and soft tissue sarcomas.2014

    • Author(s)
      Nakamura T
    • Organizer
      2014 SNUCRI Cancer Symposium
    • Place of Presentation
      Mokpo, South Korea
    • Year and Date
      2014-04-18
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Remarks] 公益財団法人がん研究会がん研究所発がん研究部

    • URL

      http://www.jfcr.or.jp/laboratory/department/carcinogenesis/index.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] がん研究会がん研究所発がん研究部

    • URL

      http://www.jfcr.or.jp/laboratory/department/carcinogenesis/research/003.html#01

    • Related Report
      2015 Annual Research Report
  • [Remarks] 骨軟部腫瘍におけるキメラ遺伝子と動物モデル

    • URL

      http://www.jfcr.or.jp/laboratory/department/carcinogenesis/research/003.html#01

    • Related Report
      2014 Annual Research Report
  • [Remarks] 新しいモデルマウスを用いてユーイング肉腫の発生母地を同定することに成功

    • URL

      http://www.jfcr.or.jp/laboratory/pickup/index.html

    • Related Report
      2014 Annual Research Report
  • [Patent(Industrial Property Rights)] プロレニン遺伝子またはプロレニン受容体遺伝子の発現を抑制する一本鎖核酸分子およびその用途2016

    • Inventor(s)
      黒田雅彦
    • Industrial Property Rights Holder
      北海道大学、株式会社ボナック、東京医科大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016-12-29
    • Related Report
      2016 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 遺伝子発現制御のための発現制御核酸分子およびその用途2016

    • Inventor(s)
      黒田雅彦、大野慎一郎
    • Industrial Property Rights Holder
      東京医科大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2016-168499
    • Filing Date
      2016-08-30
    • Related Report
      2016 Annual Research Report

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Published: 2014-04-04   Modified: 2022-02-02  

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