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Comprehensive genome analysis of aggressive neuroblastoma

Research Project

Project/Area Number 23591562
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionChiba Cancer Center (Research Institute)

Principal Investigator

OHIRA Miki  千葉県がんセンター(研究所), がんゲノム研究室, 室長 (20311384)

Co-Investigator(Renkei-kenkyūsha) NAKAGAWARA Akira  千葉県がんセンター, 病院長 (50117181)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords癌 / 神経芽腫 / マイクロアレイ / 遺伝子 / ゲノム
Research Abstract

Neuroblastoma is one of the most common cancer in children, and is known to exhibit wide ranges of clinical behavior, from spontaneous regression to highly resistant to chemotherapy. In this study, to construct better therapeutic strategies for each tumor subtype, we conducted integrated molecular profiling to find genome copy number aberrations, mRNA/miRNA expression patterns as well as epigenetic changes occurred frequently in aggressive neuroblastomas. A set of markers we found showed significant correlations with patient prognoses and could add new insights to develop a novel diagnostic system or to select suitable clinical treatment by using them.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (43 results)

All 2014 2013 2012 2011

All Journal Article (24 results) (of which Peer Reviewed: 24 results,  Open Access: 2 results) Presentation (19 results)

  • [Journal Article] Novel 1p tumour suppressor Dnmt1-associated protein 1 regulates MYCN/ataxia telangiectasia mutated/p53 pathway2014

    • Author(s)
      Yamaguchi Y, Takenobu H, Ohir a M, Nakazawa A, Yoshida S, Akita N, Shimozato O, Iwama A, Nakagawara A, Kamijo T.
    • Journal Title

      Eur J Cancer

      Volume: 50 Pages: 1555-1565

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] NCYM, a Cis-antisense gene of MYCN, encodes a de novo evolved protein that inhibits GSK3β resulting in the stabilization of MYCN in human neuroblastomas.2014

    • Author(s)
      Suenaga Y, Islam SM, Alagu J, Kaneko Y, Kato M, Tanaka Y, Kawana H, Hossain S, Matsumoto D, Yamamoto M, Shoji W, Itami M, Shibata T, Nakamura Y, Ohira M, Haraguchi S, Takatori A, Nakagawara A.
    • Journal Title

      PLoS Genet

      Volume: 10 Issue: 1 Pages: 1-14

    • DOI

      10.1371/journal.pgen.1003996

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ALK is a MYCN target gene and regulates cell migration and invasion in neuroblastoma.2013

    • Author(s)
      Hasan MK, Nafady A, Takatori A, Kishida S, Ohira M, Suenaga Y, Hossain S, Akter J, Ogura A, Nakamura Y, Kadomatsu K, Nakagawara A.
    • Journal Title

      Sci Rep

      Volume: 3 Issue: 1 Pages: 3450-3450

    • DOI

      10.1038/srep03450

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] RUNX3 interacts with MYCN and facilitates protein degradation in neuroblastoma2013

    • Author(s)
      Yu F, Gao W, Yokochi T, Suenaga Y, Ando K, Ohir a M, Nakamura Y, Nakagawara A.
    • Journal Title

      Oncogene

      Volume: 33 Pages: 2601-2609

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dependence receptor UNC5D mediates nerve growth factor depletion-induced neuroblastoma regression2013

    • Author(s)
      Zhu Y, Li Y, Haraguchi S, Yu M, Ohir a M, Ozaki T, Nakagawa A, Ushijima T, Isogai E, Koseki H, Nakamura Y, Kong C, Mehlen P, Arakawa H, Nakagawara A.
    • Journal Title

      J Clin Invest

      Volume: 123 Pages: 2935-2947

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Stronger prognostic power of the CpG island methylator phenotype than methylation of individual genes in neuroblastomas2013

    • Author(s)
      Asada K, Watanabe N, Nakamura Y, Ohir a M, Westermann F, Schwab M, Nakagawara A, Ushijima T.
    • Journal Title

      J pn J Clin Oncol

      Volume: 43 Pages: 641-645

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Novel adaptor protein Shf interacts with ALK receptor and negatively regulates its downstream signals in neuroblastoma2013

    • Author(s)
      Takagi D, Tatsumi Y, Yokochi T, Takatori A, Ohir a M, Kamijo T, Kondo S, Fujii Y, Nakagawara A.
    • Journal Title

      Cancer Sci

      Volume: 104 Pages: 563-572

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A MYCN-amplified cell line derived from a long-term event-free survivor among our sixteen established neuroblastoma cell lines2013

    • Author(s)
      Sugimoto T, Gotoh T, Yagyu S, Kuroda H, Iehara T, Hosoi H, Ohta S, Ohir a M, Nakagawara A.
    • Journal Title

      Cancer Lett

      Volume: 331 Pages: 115-121

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Temozolomide suppresses MYC via activation of TAp63 to inhibit progression of human glioblastoma.2013

    • Author(s)
      Yamaki T, Suenaga Y, Iuchi T, Alagu J, Takatori A, Itami M, Araki A, Ohira M, Inoue M, Kageyama H, Yokoi S, Saeki N, Nakagawara A.
    • Journal Title

      Sci Rep.

      Volume: 3 Issue: 1 Pages: 1160-1160

    • DOI

      10.1038/srep01160

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cell culture and Drosophila model systems define three classes of anaplastic lymphoma kinase mutations in neuroblastoma2013

    • Author(s)
      Chand D, Yamazaki Y, Ruuth K, Schönherr C, Martinsson T, Kogner P, Attiyeh EF, Maris J, Morozova O, Marra MA, Ohira M, Nakagawara A, Sandström PE, Palmer RH, Hallberg B.
    • Journal Title

      Dis Model and Mech

      Volume: 6 Pages: 373-382

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Kruppel-like factor 4 (KLF4) suppresses neuroblastoma cell growth and determines non-tumorigenic lineage differentiation2013

    • Author(s)
      Shum CK, Lau ST, Tsoi LL, Chan LK, Yam JW, Ohir a M, Nakagawara A, Tam PK, Ngan ES.
    • Journal Title

      Oncogene

      Volume: 32 Pages: 4086-4099

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] RUNX3 interacts with MYCN and facilitates protein degradation in neuroblastoma.2013

    • Author(s)
      Yu F, Gao W, Yokochi T, Suenaga Y, Ando K, Ohira M, Nakamura Y, Nakagawara A.
    • Journal Title

      Oncogene

      Volume: 33 Issue: 20 Pages: 2601-2609

    • DOI

      10.1038/onc.2013.221

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dependence receptor UNC5D mediates nerve growth factor depletion-induced neuroblastoma regression.2013

    • Author(s)
      Zhu Y, Li Y, Haraguchi S, Yu M, Ohira M, Ozaki T, Nakagawa A, Ushijima T, Isogai E, Koseki H, Nakamura Y, Kong C, Mehlen P, Arakawa H, Nakagawara A.
    • Journal Title

      J Clin Invest.

      Volume: 123 Issue: 7 Pages: 2935-47

    • DOI

      10.1172/jci65988

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stronger prognostic power of the CpG island methylator phenotype than methylation of individual genes in neuroblastomas2013

    • Author(s)
      Asada K, Watanabe N, Nakamura Y, Ohira M, Westermann F, Schwab M, Nakagawara A, Ushijima T.
    • Journal Title

      Jpn J Clin Oncol

      Volume: 43 Issue: 6 Pages: 641-645

    • DOI

      10.1093/jjco/hyt058

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel adaptor protein Shf interacts with ALK receptor and negatively regulates its downstream signals in neuroblastoma.2013

    • Author(s)
      Takagi D
    • Journal Title

      Cancer Sci

      Volume: 104 Issue: 5 Pages: 563-572

    • DOI

      10.1111/cas.12115

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A MYCN-amplified cell line derived from a long-term event-free survivor among our sixteen established neuroblastoma cell lines.2013

    • Author(s)
      Sugimoto T, Gotoh T, Yagyu S, Kuroda H, Iehara T, Hosoi H, Ohta S, Ohira M, Nakagawara A.
    • Journal Title

      Cancer Lett

      Volume: 331 Issue: 1 Pages: 115-121

    • DOI

      10.1016/j.canlet.2012.12.011

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cell culture and Drosophila model systems define three classes of anaplastic lymphoma kinase mutations in neuroblastoma.2013

    • Author(s)
      Chand D, Yamazaki Y, Ruuth K, Schönherr C, Martinsson T, Kogner P, Attiyeh EF, Maris J, Morozova O, Marra MA, Ohira M, Nakagawara A, Sandström PE, Palmer RH, Hallberg B.
    • Journal Title

      Dis Model Mech.

      Volume: 6 Pages: 373-82

    • DOI

      10.1242/dmm.010348

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] ALK fusion gene positive lung cancer and 3 cases treated with an inhibitor for ALK kinase activity2012

    • Author(s)
      Kimura H, Nakajima T, Takeuchi K, Soda M, Mano H, Iizasa T, Matsui Y, Yoshino M, Shingyoji M, Itakura M, Itami M, Ikebe D, Yokoi S, Kageyama H, Ohir a M, Nakagawara A.
    • Journal Title

      Lung Cancer

      Volume: 75 Pages: 66-72

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Kruppel-like factor 4 (KLF4) suppresses neuroblastoma cell growth and determines non-tumorigenic lineage differentiation.2012

    • Author(s)
      Shum CK, Lau ST, Tsoi LL, Chan LK, Yam JW, Ohira M, Nakagawara A, Tam PK, Ngan ES.
    • Journal Title

      Oncogene

      Volume: advance online publication Issue: 35 Pages: 4086-4099

    • DOI

      10.1038/onc.2012.437

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] ALK fusion gene positive lung cancer and 3 cases treated with an inhibitor for ALK kinase activity.2012

    • Author(s)
      Kimura H, Nakajima T, Takeuchi K, Soda M, Mano H, Iizasa T, Matsui Y, Yoshino M, Shingyoji M, Itakura M, Itami M, Ikebe D, Yokoi S, Kageyama H, Ohira M, Nakagawara A.
    • Journal Title

      Lung Cancer

      Volume: 75 Issue: 1 Pages: 66-72

    • DOI

      10.1016/j.lungcan.2011.05.027

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Expression of NLRR3 orphan receptor gene is negatively regulated by MYCN and Miz-1, and its down-regulation is associated with an unfavorable outcome in neuroblastoma2011

    • Author(s)
      Akter J, Takatori, A, Hossain S, Ozaki T, Nakazawa A, Ohir a M, Suenaga Y, Nakagawara A.
    • Journal Title

      Clin Cancer Res

      Volume: 17 Pages: 6681-6692

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel potent tumour promoter aberrantly overexpressed in most human cancers2011

    • Author(s)
      Takahashi A, Tokita H, Takahashi K, Takeoka T, Murayama K, Tomotsune D, Ohira M, Iwamatsu A, Ohara K, Yazaki K, Koda T, Nakagawara A, Tani K
    • Journal Title

      Scientific Reports

      Volume: 1(15) Issue: 1 Pages: 6-6

    • DOI

      10.1038/srep00015

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Oncogenic LMO3 collaborates with HEN2 to enhance neuroblastoma cell growth through transactivation of Mash12011

    • Author(s)
      Isogai E, Ohira M, Ozaki T, Oba S, Nakamura Y, Nakagawara A
    • Journal Title

      PLoS ONE

      Volume: 6(5) Issue: 5 Pages: e19297-e19297

    • DOI

      10.1371/journal.pone.0019297

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Expression of NLRR3 orphan receptor gene is negatively regulated by MYCN and Miz-1, and its down-regulation is associated with unfavorable outcome in neuroblastoma2011

    • Author(s)
      Akter J, Takatori A, Hossain S, Ozaki T, Nakazawa A, Ohira M, Suenaga Y, Nakagawara A
    • Journal Title

      Clin Cancer Res

      Volume: 17 Issue: 21 Pages: 6681-6692

    • DOI

      10.1158/1078-0432.ccr-11-0313

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Whole exome sequencing of 101 neuroblastomas with distinct genomic subgroups identified significantly mutated pathways in aggressive tumor subtypes2013

    • Author(s)
      大平美紀, 他11名
    • Organizer
      米国癌学会小児癌分科会(AACR Special Conference on Pediatric Cancer At The Crossroads (AACR -PCAC))2013
    • Place of Presentation
      米国・サンディエゴ
    • Related Report
      2013 Final Research Report
  • [Presentation] 網羅的ゲノム解析を用いたMYCN非増幅型難治性神経芽腫の予後関連ゲノム異常の検索2013

    • Author(s)
      大平美紀, 他8名
    • Organizer
      第55回日本小児血液・がん学会学術集会
    • Place of Presentation
      福岡
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] 難治性中間型神経芽腫の予後に関与するゲノムプロファイルの検索2013

    • Author(s)
      大平美紀, 他7名
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] Risk classification of neuroblastoma based on genomic profiles : For future tailor-made therapeutic strategies in Japan2013

    • Author(s)
      大平美紀, 他10名
    • Organizer
      第45回国際小児がん学会(SIOP2013)
    • Place of Presentation
      中国・香港
    • Related Report
      2013 Final Research Report
  • [Presentation] Prognosis-related miRNA expression profiles of neuroblastoma2013

    • Author(s)
      大平美紀, 他4名
    • Organizer
      第104回米国癌学会総会(AACR2013)
    • Place of Presentation
      米国・ワシントンD.C.
    • Related Report
      2013 Final Research Report
  • [Presentation] Prognosis-related miRNA expression profiles of neuroblastoma Short title: miRNA expression in neuroblastoma2013

    • Author(s)
      M.Ohira, E.Isogai, Y.Nakamura, T.Kamijo, A.Nakagawara
    • Organizer
      第104回米国癌学会総会(AACR2013)
    • Place of Presentation
      米国・ワシントンD.C.
    • Related Report
      2013 Annual Research Report
  • [Presentation] Risk classification of neuroblastoma based on genomic profiles: For future tailor-made therapeutic strategies in Japan2013

    • Author(s)
      M.Ohira, T.Kamijo, Y.Nakamura, K.Matsumoto, M.Kumagai, A.Nakazawa, T.Takimoto, T.Fukushima, T.Tajiri, H.Ikeda, A.Nakagawara
    • Organizer
      第45回国際小児がん学会(SIOP2013)
    • Place of Presentation
      中国・香港
    • Related Report
      2013 Annual Research Report
  • [Presentation] Whole exome sequencing of 101 neuroblastomas with distinct genomic subgroups identified significantly mutated pathways in aggressive tumor subtypes2013

    • Author(s)
      M.Ohira, Y.Li, Y.Zhou, X.Li, Z.Gao, K.Tatsuno, S.Tsutsumi, S.Yamamoto, Y.Nakamura, T.Kamijo, H.Aburatani, A.Nakagawara
    • Organizer
      AACR Special Conference on Pediatric Cancer At The Crossroads (AACR-PCAC)
    • Place of Presentation
      米国・サンディエゴ
    • Related Report
      2013 Annual Research Report
  • [Presentation] マイクロRNA発現レベルによる神経芽腫のリスク分類2012

    • Author(s)
      大平美紀, 他4名
    • Organizer
      第54回日本小児血液・がん学会学術集会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] Prognosis prediction of neuroblastoma subsets based on miRNA expression profiles2012

    • Author(s)
      大平美紀, 他4名
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] 神経芽腫の予後マーカーとしてのmiRNA発現プロファイル2012

    • Author(s)
      大平美紀, 他4名
    • Organizer
      第19回日本遺伝子診療学会大会
    • Place of Presentation
      千葉
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] Gene expression and genomic aberration signatures cooperatively work to improve tumor risk stratification of neuroblastoma2012

    • Author(s)
      大平美紀, 他3名
    • Organizer
      Advances in Neuroblastoma Research 2012 (ANR2012)
    • Place of Presentation
      カナダ・トロント
    • Related Report
      2013 Final Research Report
  • [Presentation] miRNA expression levels are strongly correlated with neuroblastoma prognosis2012

    • Author(s)
      大平美紀, 他4名
    • Organizer
      第2回日中がん研究シンポジウム
    • Place of Presentation
      千葉
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] Gene expression and genomic aberration signatures cooperatively work to improve tumor risk stratification of neuroblastoma.2012

    • Author(s)
      Ohira M, Nakamura Y, Kamijo T, Nakagawara A.
    • Organizer
      Advances in Neuroblastoma Research 2012
    • Place of Presentation
      カナダ・トロント
    • Related Report
      2012 Research-status Report
  • [Presentation] 神経芽腫の予後に相関するマイクロRNA発現パターンの検索2011

    • Author(s)
      大平美紀, 他4名
    • Organizer
      第53回日本小児血液・がん学会学術集会
    • Place of Presentation
      新前橋
    • Related Report
      2013 Final Research Report 2011 Research-status Report
  • [Presentation] LIM-only protein LMO3は、神経芽腫の発生母地である神経堤細胞において細胞増殖と分化を制御する2011

    • Author(s)
      大平美紀, 他3名
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Final Research Report
  • [Presentation] 神経芽腫の予後に強く相関するmiRNA発現プロファイルの検索2011

    • Author(s)
      大平美紀, 他4名
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Final Research Report
  • [Presentation] Identification of prognosis-related miRNA expression profiles in neuroblastoma.2011

    • Author(s)
      Ohira M, Isogai E, Nakamura Y, Kamijo T, Nakagawara A.
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Research-status Report
  • [Presentation] The LIM-only protein LMO3 could regulate growth and proliferation in neural crest cells.2011

    • Author(s)
      Isogai E, Ohira M, Haraguchi S, Nakagawara A.
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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