Screening for the genes which shows synergistic phenotype with MYCN-With the aim of new molecular target of neuroblastoma

• Project/Area Number: 24590376
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Aichi Cancer Center Research Institute
• Principal Investigator: MURAKAMI-TONAMI Yuko 愛知県がんセンター(研究所), 分子腫瘍学部, 主任研究員 (70405174)
• Co-Investigator(Kenkyū-buntansha): KADOMATSU Kenji 名古屋大学, 大学院医学系研究科・生物化学講座分子生物学, 教授 (80204519)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 神経芽腫 / 合成致死 / DNA損傷修復 / MYCN / DNA損傷応答

Outline of Final Research Achievements

We identified SMC2, a subunit of condensin complex, as a candidate gene which shows synergistic lethal phenotype with MYCN amplification/overexpression. In addition, we found SMC2 regulates expression of DNA repair genes cooperation with MYCN (Cell Cycle, 13 (7) : 1115-31, 2014). To find further candidate genes, we screened for the genes which showed synthetic lethal phenotype with MYCN overexpression using shRNA library in neuroblastoma cells. We also improved the method of discovering combinational interactions using survival data (Bioinformatics, 29 (23) : 3053-59, 2013).

Research Products

• [Journal Article] The nucleolar protein PES1 is a marker of neuroblastoma outcome and is associated with neuroblastoma differentiation. (2015)
  • Author(s): Nakaguro M, Kiyonari S, Kishida S, Cao D, Murakami-Tonami Y, Ichikawa H, Takeuchi I, Nakamura S, Kadomatsu K
  • Journal Title: Cancer Science Volume: 106 Issue: 3 Pages: 237-243
  • DOI: 10.1111/cas.12598
  • Peer Reviewed / Open Access
• [Journal Article] Regulation of wee1(+) expression during meiosis in fission yeast. (2014)
  • Author(s): Murakami-Tonami Y, Ohtsuka H, Aiba H, Murakami H.
  • Journal Title: Cell Cycle. Volume: 13 Issue: 18 Pages: 2853-2858
  • DOI: 10.4161/15384101.2014.946807
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Inactivation of SMC2 shows a synergistic lethal response in MYCN-amplified neuroblastoma cells. (2014)
  • Author(s): Murakami-Tonami Y, Kishida S, Takeuchi I, Katou Y, Maris JM, Ichikawa H, Kondo Y, Sekido Y, Shirahige K, Murakami H, Kadomatsu K.
  • Journal Title: Cell Cycle. Volume: 13 Issue: 7 Pages: 1115-1131
  • DOI: 10.4161/cc.27983
  • Peer Reviewed / Open Access
• [Journal Article] Discovering combinatorial interactions in survival data (2013)
  • Author(s): David duVerle, Ichiro Takeuchi, Yuko Murakami-Tonami, Kenji kadomatsu, Koji Tsuda
  • Journal Title: Bio in formatics Volume: 23 Issue: 23 Pages: 3053-3059
  • DOI: 10.1093/bioinformatics/btt532
  • Peer Reviewed
• [Presentation] SGO1はMYCNがん遺伝子増幅細胞においてDNA損傷応答を制御する (2014)
  • Author(s): 村上（渡並）優子
  • Organizer: 日本分子生物学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-11-26
• [Presentation] MYCN増幅と合成致死表現型を示す遺伝子の探索～神経芽腫をモデルとして (2014)
  • Author(s): 村上（渡並）優子
  • Organizer: 日本薬学会東海支部特別講演会
  • Place of Presentation: 金城学院大学薬学部
  • Year and Date: 2014-07-16
  • Invited
• [Presentation] Inactivation of SMC2 shows a synergistic lethal response in MYCN-amplified neuroblastoma cells. (2014)
  • Author(s): Yuko Murakami-Tonami
  • Organizer: Advances in Neuroblastoma Research Congress
  • Place of Presentation: ケルン（ドイツ）
  • Year and Date: 2014-05-15
• [Presentation] Inactivation of Smc2 shows synergistic lethal response to MYCN amplification by regulating DNA damage response genes transcription in neuroblastoma cells. (2013)
  • Author(s): Yuko Murakami-Tonami
  • Organizer: EMBO conference (The DNA damage response in cell physiology and disease)
  • Place of Presentation: Cape Sounio（アテネ市、ギリシア）
• [Presentation] SMC2はDNA損傷修復に関連する遺伝子の転写を制御する (2013)
  • Author(s): 村上（渡並）優子
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド（神戸市）
• [Presentation] Inactivation of hSgo1 shows synthetic phenotype to MYCN amplification.
  • Author(s): Yuko Murakami-Tonami, Satoshi Kishida, Kenji Kadomatsu
  • Organizer: Advances in neuroblastoma research conference 2012
  • Place of Presentation: Fairmont Royal York Hotel（トロント）
• [Presentation] Smc2はDNA修復因子の転写制御を介してMYCNとSyntheticな表現型を示す
  • Author(s): 村上（渡並）優子、岸田聡、門松健治
  • Organizer: 第35回分子生物学会年会
  • Place of Presentation: 福岡国際会議場（福岡）
• [Patent(Industrial Property Rights)] MYCN増幅型疾患のための分子標的およびその利用 (2012)
  • Inventor(s): 村上（渡並）優子、門松健治
  • Industrial Property Rights Holder: 名古屋大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2012-05-01