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Integrated genomic analysis of aggressive subtype of neuroblastoma

Research Project

Project/Area Number 26461603
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionResearch Institute for Clinical Oncology, Saitama Cancer Center (2015-2016)
Chiba Cancer Center (Research Institute) (2014)

Principal Investigator

Ohira Miki  埼玉県立がんセンター(臨床腫瘍研究所), 臨床腫瘍研究所, 主幹研究員 (20311384)

Co-Investigator(Renkei-kenkyūsha) NAKAGAWARA Akira  佐賀県医療センター好生館, 理事長 (50117181)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords神経芽腫 / ゲノム / 遺伝子 / マイクロアレイ / 癌
Outline of Final Research Achievements

Neuroblastoma (NB) is the most common pediatric extracranial solid tumor, originating from the sympathoadrenal lineage of neural crest. Despite intense multi-modal therapy, NB remains the second most common cause of cancer deaths among children. To elucidate molecular basis for malignant type of NB, we have conducted integrated genomic analyses, including array CGH, whole exome sequencing, transcriptome and methylome profiling. Whole exome sequencing of 30 high stage primary tumors identified approximately 20 non-silent somatic mutations and indels per tumor in average, among which 27 were recurrent mutations appeared >2. Pathway analysis revealed enrichment of the mutated genes in the MAPK pathway and the axon guidance pathway. Methylome profiling suggested the existence of three clusters with different survival rates. Altogether, these genomic features can help understand NB pathogenesis and contribute risk stratification for therapy.

Report

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

    (23 results)

All 2017 2016 2015 2014

All Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 9 results,  Open Access: 8 results,  Acknowledgement Compliant: 2 results) Presentation (14 results) (of which Int'l Joint Research: 5 results)

  • [Journal Article] Genomic analysis-integrated whole-exome sequencing of neuroblastoma identifies genetic mutations in axon guidance pathway.2017

    • Author(s)
      Li Y*, Ohira M*, Zhou Y, Xiong T, luo W, Yang C, Li X, Gao Z, Nakamura Y, Kamijo T, Kaneko Y, Taketani T, Ueyama J, Tajiri T, Zhang H, Wang J, Yang H, Yin Y, Nakagawara A.
    • Journal Title

      Oncotarget

      Volume: 印刷中

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Transcriptional regulation of BMCC1 mediated by E2F1 in neuroblastoma cells2016

    • Author(s)
      Mohammad Sazzadul Islam, Yasutoshi Tatsumi, Ryo Takano, Tomoki Yokochi, Jesmin Akter, Toshinori Ozaki, Yohko Nakamura, Miki Ohira, and Akira Nakagawara
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 478 Issue: 1 Pages: 81-86

    • DOI

      10.1016/j.bbrc.2016.07.089

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Neuronal leucine-rich repeat 1 negatively regulates anaplastic lymphoma kinase in neuroblastoma.2016

    • Author(s)
      Satoh S, Takatori A, Ogura A, Kohashi K, Souzaki R, Kinoshita Y, Taguchi T, Hossain MS, Ohira M, Nakamura Y, Nakagawara A.
    • Journal Title

      Sci Rep.

      Volume: 6 Issue: 1 Pages: 32682-32682

    • DOI

      10.1038/srep32682

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Revised risk estimation and treatment stratification of low- and intermediate-risk neuroblastoma patients by integrating clinical and molecular prognostic markers.2015

    • Author(s)
      Oberthuer A, Juraeva D, Hero B, Volland R, Carolina S, Schmidt R, Faldum A, Kahlert Y, Engesser A, Asgharzadeh S, Seeger RC, Ohira M, Nakagawara A, Scaruffi P, at all
    • Journal Title

      Clin Cancer Res.

      Volume: 21(8) Issue: 8 Pages: 1904-1915

    • DOI

      10.1158/1078-0432.ccr-14-0817

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Correlation between the International Neuroblastoma Pathology Classification and genomic signature in neuroblastoma2015

    • Author(s)
      Nakazawa A, Haga C, Ohira M, Okita H, Kamijo T, Nakagawara A.
    • Journal Title

      Cancer Sci.

      Volume: 未定 Issue: 6 Pages: 766-771

    • DOI

      10.1111/cas.12665

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Functional interplay between MYCN, NCYM and OCT4 promotes aggressiveness of human neuroblastomas.2015

    • Author(s)
      Kaneko Y, Suenaga Y, Islam SM, Matsumoto D, Nakamura Y, Ohira M, Yokoi S, Nakagawara A.
    • Journal Title

      Cancer Sci.

      Volume: 10 Issue: 7 Pages: 12677-12677

    • DOI

      10.1111/cas.12677

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oncogenic <i>Lmo3</i> cooperates with <i>Hen2</i> to induce hydrocephalus in mice2015

    • Author(s)
      Isogai E, Okumura K ,Saito M, Yoshizawa Y, Itoh K, Tando S, Ohira M, Haraguchi S, Nakagawara A, Fushiki S, Nagase H, Wakabayashi Y
    • Journal Title

      Experimental Animals

      Volume: 64 Issue: 4 Pages: 407-414

    • DOI

      10.1538/expanim.15-0026

    • NAID

      130005104844

    • ISSN
      0007-5124, 1341-1357, 1881-7122
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sendai virus-mediated expression of reprogramming factors promotes plasticity of human neuroblastoma cells.2015

    • Author(s)
      Islam SM, Suenaga Y, Takatori A, Ueda Y, Kaneko Y, Kawana H, Itami M, Ohira M, Yokoi S, Nakagawara A.
    • Journal Title

      Cancer Sci.

      Volume: 106 Issue: 10 Pages: 1351-1361

    • DOI

      10.1111/cas.12746

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Flotillin-1 regulates oncogenic signaling in neuroblastoma cells by regulating ALK membrane association.2014

    • Author(s)
      Tomiyama A, Uekita T, Kamata R, Sasaki K, Takita J, Ohira M, Nakagawara A, Kitanaka C, Mori K, Yamaguchi H, Sakai R.
    • Journal Title

      Cancer Res.

      Volume: 74(14) Issue: 14 Pages: 3790-3801

    • DOI

      10.1158/0008-5472.can-14-0241

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 難治性神経芽腫のゲノム・エピゲノム統合解析2016

    • Author(s)
      大平美紀、巽 康年、中村洋子、辰野健二、堤 修一、山本尚吾、永江玄太、Claire Renard-Guillet、杉野隆一、永瀬浩喜、上條岳彦、油谷浩幸、中川原 章
    • Organizer
      第58回日本小児血液・がん学会学術集会
    • Place of Presentation
      品川
    • Year and Date
      2016-12-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] 国際リスク分類システムと連携した神経芽腫分子生物学的データベースの構築と高リスク神経芽腫のゲノム解析2016

    • Author(s)
      大平美紀、上條岳彦、瀧本哲也、中澤温子、松本公一、七野浩之、菱木知郎、家原知子、中村洋子、永瀬浩喜、米田光宏、福島 敬、田尻達郎、中川原 章
    • Organizer
      第58回日本小児血液・がん学会学術集会
    • Place of Presentation
      品川
    • Year and Date
      2016-12-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] 難治性神経芽腫の網羅的ゲノム・エピゲノムプロファイル2016

    • Author(s)
      大平美紀、巽 康年、中村洋子、辰野健二、堤 修一、山本尚吾、永江玄太、Renard-Guillet Claire 、杉野隆一、永瀬浩喜、上條岳彦、油谷浩幸、中川原 章
    • 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
  • [Presentation] Clinical relevance of genomic and epigenomic classification of MYCN-non-amplified neuroblastoma2016

    • Author(s)
      Ohira M, Nakamura Y, Tatsumi Y, Tatsuno K, Tsutsumi S, Yamamoto S, Nagae G, Renard-Guillet C, Nagase H, Kamijo T, Aburatani H, Nakagawara A
    • Organizer
      ANR2016
    • Place of Presentation
      ケアンズ(オーストラリア)
    • Year and Date
      2016-06-19
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Genomic characterization of high-risk neuroblastoma in Japan: A retrospective study of 537 cases by using updated follow-up data based on INRG variables [JNBSG (Japan Neuroblastoma Study Group)]2016

    • Author(s)
      Ohira M, Kamijo T, Takimoto T, Nakazawa A, Matsumoto K, Shichino H, Hishiki T, Iehara T, Nakamura Y, Nagase H, Yoneda A, Fukushima T, Tajiri T, Nakagawara A
    • Organizer
      ANR2016
    • Place of Presentation
      ケアンズ( オーストラリア)
    • Year and Date
      2016-06-19
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Genomic landscape of aggressive tumor subtype in MYCN-non-amplified neuroblastoma2016

    • Author(s)
      Ohira M, Tatsuno K, Nakamura Y, Tatsumi Y, Tsutsumi S, Yamamoto S, Nagae G, Renard-Guillet C, Nagase H, Kamijo T, Aburatani H, Nakagawara A
    • Organizer
      AACR Annual Meeting 2016
    • Place of Presentation
      ニューオーリンズ(米国)
    • Year and Date
      2016-04-16
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Genomic profiling of intermediate risk type of neuroblastoma without MYCN amplification.2015

    • Author(s)
      M.Ohira, Y.Nakamura, K.Tatsuno, S.Tsutsumi, S.Yamamoto, G.Nagae, Y.Tatsumi, H.Nagase, T.Kamijo, H.Aburatani, A.Nakagawara.
    • Organizer
      第57回日本小児血液・がん学会学術集会
    • Place of Presentation
      甲府市
    • Year and Date
      2015-11-27
    • Related Report
      2015 Research-status Report
  • [Presentation] Genomic characterization of aggressive subtypes of neuroblastoma with 11q partial loss.2015

    • Author(s)
      M.Ohira, Y.Nakamura, K.Tatsuno, S.Tsutsumi, S.Yamamoto, G.Nagae, Y.Tatsumi, H.Nagase, T.Kamijo, H.Aburatani, A.Nakagawara.
    • Organizer
      神経芽腫アジアパシフィックシンポジウム2015
    • Place of Presentation
      台湾・台北市
    • Year and Date
      2015-11-13
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 11q欠失を伴った難治性中間リスク型神経芽腫のゲノム・エピゲノム解析.2015

    • Author(s)
      大平美紀, 中村洋子, 辰野健二, 堤修一, 山本尚吾, 永江玄太, 巽康年, 永瀬浩喜,上條岳彦, 油谷浩幸, 中川原章.
    • Organizer
      第74回日本癌学会学術集会
    • Place of Presentation
      名古屋市
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] Comprehensive genomic characterization of aggressive subtype of neuroblastoma without MYCN amplification.2015

    • Author(s)
      M.Ohira, K.Tatsuno, S.Tsutsumi, S.Yamamoto, Y.Nakamura, T.Kamijo, H.Aburatani, A.Nakagawara.
    • Organizer
      第106回米国癌学会総会(AACR2014)
    • Place of Presentation
      米国・フィラデルフィア
    • Year and Date
      2015-04-18
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 神経芽腫難治性サブタイプの網羅的ゲノム解析による予後関連ゲノム異常の検索2014

    • Author(s)
      大平美紀, 辰野健二, 堤修一, 山本尚吾, 中村洋子, 上條岳彦, 油谷浩幸, 中川原章
    • Organizer
      第56回日本小児血液・がん学会学術集会
    • Place of Presentation
      岡山
    • Year and Date
      2014-11-28 – 2014-11-30
    • Related Report
      2014 Research-status Report
  • [Presentation] 半導体次世代シーケンサーを用いたがん臨床検体のゲノムシーケンシング2014

    • Author(s)
      巽 康年、丸 喜明、中村友紀、大平美紀、伊丹真紀子、片山 稔、横井左奈、永瀬浩喜
    • Organizer
      第73回日本癌学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] 進行神経芽腫の次世代シーケンサーによる全エクソーム解析2014

    • Author(s)
      大平美紀, 李元元, 辰野健二, 堤修一, 山本尚吾, 中村洋子, 上條岳彦, 油谷浩幸, 中川原章
    • Organizer
      第73回日本癌学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Genome-based sub-classification of neuroblastoma:A retrospective study by using 573 neuroblastoma samples obtained in Japan2014

    • Author(s)
      M.Ohira, T.Kamijo, Y.Nakamura,T.Takimoto, A.Nakagzawa, J.Takita, T.Iehara, H.Takahashi, T.Tajiri, Akira Nakagawara:Japan Neurobastoma Study Group.
    • Organizer
      Advances in Neuroblastoma Research Congress 2014
    • Place of Presentation
      ドイツ・ケルン
    • Year and Date
      2014-05-13 – 2014-05-16
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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