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iPS-derived differentiation-related tumor models and multi-omics analysis

Research Project

Project/Area Number 17K19623
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Tumor biology and related fields
Research InstitutionResearch Institute for Clinical Oncology, Saitama Cancer Center

Principal Investigator

Kamijo Takehiko  埼玉県立がんセンター(臨床腫瘍研究所), 臨床腫瘍研究所, 所長 (90262708)

Co-Investigator(Kenkyū-buntansha) 大平 美紀  埼玉県立がんセンター(臨床腫瘍研究所), 臨床腫瘍研究所, 研究員 (20311384)
杉野 隆一  埼玉県立がんセンター(臨床腫瘍研究所), 臨床腫瘍研究所, 研究員 (90749516)
Research Collaborator Mukai Kyousuke  
Takenobu Hisanori  
Yamada Yasuhiro  
Jesmin Akter  
Project Period (FY) 2017-06-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
KeywordsiPS / 小児がん / 神経芽腫 / オミックス解析 / エピゲノム / 発がんモデル / 発生・分化 / 癌
Outline of Final Research Achievements

We established 3 wild-type and 1 Li-Fraumeni syndrome patient-derived neural crest cells (NCC) from iPS cells and confirmed the differentiation by FACS analysis using NCC marker p75 antibody, suggesting > 90 % differentiation. We performed multi-omics analysis including transcriptome, DNA methylome, and ChIP sequence of histone codes to study the differentiation mechanism related to tumorigenesis. Transformation of the NCCs were successfully performed by MYCN oncogene expression and soft agar colony formation experiments. Tumor formation in immune-deficient mice was studied and omics analysis is ongoing.

Academic Significance and Societal Importance of the Research Achievements

MYCN遺伝子を時間的(iPSからの分化誘導のタイムコース)・空間的(iPSからの神経堤細胞および交感神経細胞への分化誘導)に誘導する系は、神経芽腫発がん機構の解析に大きな進歩をもたらし、かつ新たな治療標的検出につながる研究と考えられる。更に、MYCN遺伝子発現異常による難治性がん(神経芽腫、脳腫瘍、小児腫瘍)の治療法を開発するためにも有用であり、従来の腫瘍細胞での遺伝子発現やトランスジェニックマウスでは不可能であった遺伝子発現誘導システムを構築して解析する研究である。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (17 results)

All 2019 2018 2017 Other

All Journal Article (10 results) (of which Int'l Joint Research: 10 results,  Peer Reviewed: 10 results,  Open Access: 9 results) Presentation (6 results) (of which Int'l Joint Research: 5 results) Remarks (1 results)

  • [Journal Article] Combined Genetic and Chromosomal Characterization of Wilms Tumors Identifies Chromosome 12 Gain as a Potential New Marker Predicting a Favorable Outcome2019

    • Author(s)
      Haruta Masayuki、Arai Yasuhito、Okita Hajime、Tanaka Yukichi、Takimoto Tetsuya、Sugino Ryuichi P.、Yamada Yasuhiro、Kamijo Takehiko、Oue Takaharu、Fukuzawa Masahiro、Koshinaga Tsugumichi、Kaneko Yasuhiko
    • Journal Title

      Neoplasia

      Volume: 21 Issue: 1 Pages: 117-131

    • DOI

      10.1016/j.neo.2018.10.007

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A Polymorphic Variant in p19Arf Confers Resistance to Chemically Induced Skin Tumors by Activating the p53 Pathway2019

    • Author(s)
      Saito M, Okumura K, Isogai E, Araki K, Tanikawa C, Matsuda K, Kamijo T, Kominami R, Wakabayashi Y.
    • Journal Title

      Journal of Investigative Dermatology

      Volume: in press Issue: 7 Pages: 30032-6

    • DOI

      10.1016/j.jid.2018.12.027

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Recycling endosomal CD133 functions as an inhibitor of autophagy at the pericentrosomal region2019

    • Author(s)
      Hideki Izumi, Yuanyuan Li, Masami Shibaki, Daisuke Mori, Michio Yasunami, Seiji Sato, Hisashi Matsunaga, Takao Mae, Kenji Kodama, Takehiko Kamijo, Yasuhiko Kaneko & Akira Nakagawara
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 2236-2236

    • DOI

      10.1038/s41598-019-39229-8

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] EZH2 regulates neuroblastoma cell differentiation via NTRK1 promoter epigenetic modifications2018

    • Author(s)
      Li Zhenghao、Takenobu Hisanori、Setyawati Amallia Nuggetsiana、Akita Nobuhiro、Haruta Masayuki、Satoh Shunpei、Shinno Yoshitaka、Chikaraishi Koji、Mukae Kyosuke、Akter Jesmin、Sugino Ryuichi P.、Nakazawa Atsuko、Nakagawara Akira、Aburatani Hiroyuki、Ohira Miki、Kamijo Takehiko
    • Journal Title

      Oncogene

      Volume: 37 Issue: 20 Pages: 2714-2727

    • DOI

      10.1038/s41388-018-0133-3

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Results of a phase II trial for high-risk neuroblastoma treatment protocol JN-H-07: a report from the Japan Childhood Cancer Group Neuroblastoma Committee (JNBSG)2018

    • Author(s)
      Hishiki T、For the Japan Childhood Cancer Group Neuroblastoma Committee (JNBSG)、Matsumoto K、Ohira M、Kamijo T、Shichino H、Kuroda T、Yoneda A、Soejima T、Nakazawa A、Takimoto T、Yokota I、Teramukai S、Takahashi H、Fukushima T、Kaneko T、Hara J、Kaneko M、Ikeda H、Tajiri T、Nakagawara A
    • Journal Title

      International Journal of Clinical Oncology

      Volume: 23 Issue: 5 Pages: 965-973

    • DOI

      10.1007/s10147-018-1281-8

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of the genetic and clinical characteristics of neuroblastomas using genome-wide analysis2017

    • Author(s)
      Uryu K, Nishimura R, Kataoka K, Sato Y, Nakazawa A, Suzuki H, Yoshida K, Seki M, Hiwatari M, Isobe T, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Koh K, Hanada R, Oka A, Hayashi Y, Ohira M, Kamijo T, Nagase H, Takimoto T, Tajiri T, Nakagawara A, Ogawa S, Takita J
    • Journal Title

      Oncotarget

      Volume: 8 Issue: 64 Pages: 107513-107529

    • DOI

      10.18632/oncotarget.22495

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Neurocan, an extracellular chondroitin sulfate proteoglycan, stimulates neuroblastoma cells to promote malignant phenotypes.2017

    • Author(s)
      1.Su Z, Kishida S, Tsubota S, Sakamoto K, Cao D, Kiyonari S, Ohira M, Kamijo T, Narita A, Xu Y, Takahashi Y, Kadomatsu K.
    • Journal Title

      Oncotarget

      Volume: 8 Issue: 63 Pages: 106296-106310

    • DOI

      10.18632/oncotarget.22435

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Genomic analysis–integrated whole-exome sequencing of neuroblastomas identifies genetic mutations in axon guidance pathway2017

    • Author(s)
      Li Yuanyuan、Ohira Miki、Zhou Yong、Xiong Teng、Luo Wen、Yang Chao、Li Xiangchun、Gao Zhibo、Zhou Rui、Nakamura Yohko、Kamijo Takehiko、Kaneko Yasuhiko、Taketani Takeshi、Ueyama Junichi、Tajiri Tatsuro、Zhang Hongyan、Wang Jian、Yang Huanming、Yin Ye、Nakagawara Akira
    • Journal Title

      Oncotarget

      Volume: 8 Issue: 34 Pages: 56684-56697

    • DOI

      10.18632/oncotarget.18079

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CFC1 is a cancer stemness-regulating factor in neuroblastoma2017

    • Author(s)
      Chikaraishi Koji、Takenobu Hisanori、Sugino Ryuichi P.、Mukae Kyosuke、Akter Jesmin、Haruta Masayuki、Kurosumi Masafumi、Endo Takaho A.、Koseki Haruhiko、Shimojo Naoki、Ohira Miki、Kamijo Takehiko
    • Journal Title

      Oncotarget

      Volume: 8 Issue: 28 Pages: 45046-45059

    • DOI

      10.18632/oncotarget.18464

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cancer-type OATP1B3 mRNA has the potential to become a detection and prognostic biomarker for human colorectal cancer.2017

    • Author(s)
      Sun Y, Harada M, Shimozato O, Souda H, Takiguchi N, Nabeya Y, Kamijo T, Akita H, Anzai N, Chiba K, Furihata T.
    • Journal Title

      Biomark Med.

      Volume: 印刷中 Issue: 8 Pages: 629-639

    • DOI

      10.2217/bmm-2017-0098

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 1.Genome and epigenome profiling of high stage neuroblastoma2018

    • Author(s)
      Miki Ohira, Ryuichi Sugino, Hisanori Takenobu, Zhenghao Li, Masayuki Haruta, Genta Nagae, Claire Renard-Guillet, Akira Nakagawara, Hiroyuki Aburatani, Takehiko Kamijo
    • Organizer
      AACR2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 2.CDX1 regulates neuroblastoma stemness through MYC pathway modulation and reprogramming gene activation2018

    • Author(s)
      Hisanori Takenobu, Miki Ohira, Ryuichi Sugino, Koji Chikaraishi, Kyosuke Mukae, Nobuhiro Akita, Masayuki Haruta, Akira Nakagawara, Manabu Nakayama, Haruhiko Koseki, Takehiko Kamijo
    • Organizer
      ANR2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 3.Reevaluation of PDGFRα signal in neuroblastoma: high expression and a new nonsynonymous mutation2018

    • Author(s)
      Shunpei Satoh, Miki Ohira, Hisanori Takenobu, Akira Nakagawara, Takehiko Kamijo
    • Organizer
      ANR2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 4.Genomic characterization of high-risk/ultra-high-risk neuroblastomas found in 610 patients registered in Japan Children’s Study Group Neuroblastoma Committee (JCCG-JNBSG)2018

    • Author(s)
      M Ohira, T Kamijo, R P Sugino, M Haruta, H Takenobu T Takimoto, A Nakazawa, T Hishiki, K Matsumoto, H Shichino, T Ushijima, T Iehara, Y Nakamura, H Nagase, J Takita, A Yoneda, Ti Fukushima, T Tajiri, A Nakagawara, Japan Children’s Cancer Group Neuroblastoma Committee (JCCG-JNBSG)
    • Organizer
      ANR2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 5.CFC1 is a cancer stemness-regulating factor in neuroblastoma.2018

    • Author(s)
      Chikaraishi K, Takenobu H, Sugino RP, Mukae K, Akter J, Haruta M, Kurosumi M, Endo TA, Koseki H, Shimojo N, Ohira M, Kamijo T.
    • Organizer
      ANR2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effects of development regulators on neuroblastoma biology2017

    • Author(s)
      Takehiko Kamijo
    • Organizer
      The 75th Annual Meeting of the Japanese Cancer Association
    • Related Report
      2017 Research-status Report
  • [Remarks] 埼玉県立がんセンター 臨床腫瘍研究所

    • URL

      https://www.pref.saitama.lg.jp/saitama-cc/kenkyujo/kenkyujo.html

    • Related Report
      2018 Annual Research Report

URL: 

Published: 2017-07-21   Modified: 2021-01-27  

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