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Investigation of the significance of alteration in gene promoter methylations for the cause of intratumoral heterogeneity of the expression levels of HER2.

Research Project

Project/Area Number 25860266
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Human pathology
Research InstitutionKanazawa University

Principal Investigator

OYAMA Takeru  金沢大学, 医学系, 助教 (00515314)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
KeywordsCGH / gastric cancer / heterogeneity / HER2 / ERBB2 / NEU / array CGH / epigenetics / methylation / LCM
Outline of Final Research Achievements

The tumors with intratumoral heterogeneity of HER2 protein were selected from the surgical specimens of HER2 positive advanced gastric cancer. Total RNA were isolated from both HER2 positive and HER2 negative area in a tumor. Whole genome comparative analyses using gene expression arrays of these RNA revealed that the expression levels of some gene including apoptosis associated genes were more than four times as high as those in the other area. The results of these gene expression levels were attempted to be validate by quantitative real-time RT-PCR, but failed to confirm the values of these gene expressions. This might be due to RNA degradation by aging of the tissues and/or formalin fixation. To acquire more reproducible data, Genome-Wide human SNP array analyses were performed on the genomic DNA from the two areas. These analyses revealed the difference in the gene copy number of some genes including a homeobox as were confirmed using fluolecence in situ hybridization.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (15 results)

All 2015 2014 2013

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (12 results)

  • [Journal Article] Semi-comprehensive analysis of gene amplification in gastric cancers using multiplex ligation-dependent probe amplification and fluorescence in situ hybridization.2015

    • Author(s)
      Ooi A, Oyama T, Nakamura R, Tajiri R, Ikeda H, Fushida Y, Nakamura H, Dobashi Y.
    • Journal Title

      Modern Pathology

      Volume: in press Issue: 6 Pages: 861-871

    • DOI

      10.1038/modpathol.2015.33

    • NAID

      120005593968

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intratumoral heterogeneous amplification of ERBB2 and subclonal genetic diversity in gastric cancers revealed by multiple ligation-dependent probe amplification and fluorescence in situ hybridization.2014

    • Author(s)
      Tajiri. R., Ooi. A., Fujimura, T., Dobashi, Y., Oyama, T., Nakamura, R. and Ikeda, H.
    • Journal Title

      Hum Pathol.

      Volume: 45(4) Issue: 4 Pages: 725-34

    • DOI

      10.1016/j.humpath.2013.11.004

    • NAID

      120005440337

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clonal profiling of mixed lobular and ductal carcinoma revealed by multiplex ligation-dependent probe amplification and fluorescence in situ hybridization2014

    • Author(s)
      Tajiri R, Inokuchi M, Sawada-Kitamura S, Kawashima H, Nakamura R, Oyama T, Dobashi Y, Ooi A
    • Journal Title

      Pathol Int

      Volume: 64 Issue: 5 Pages: 231-236

    • DOI

      10.1111/pin.12158

    • NAID

      120005463366

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] アレイCGH法による癌関連遺伝子発現の腫瘍内ヘテロ不均一性を示す部分間におけるゲノムコピー数異常解析2014

    • Author(s)
      尾山 武、中村 律子、田尻 亮輔、大井 章史
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜、横浜
    • Year and Date
      2014-09-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] MLPAとFISHを用いた胃癌における増幅遺伝子の準網羅的検索2014

    • Author(s)
      2.大井 章史、田尻 亮輔、尾山 武、中村 律子、伏田 幸夫、土橋 洋
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜、横浜
    • Year and Date
      2014-09-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] FISH法を用いた膀胱尿路上皮癌におけるCCND1遺伝子増幅の検索2014

    • Author(s)
      田尻 亮輔、尾山 武、中村 律子、大井 章史
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜、横浜
    • Year and Date
      2014-09-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] Multiple ligation-dependent probe amplificationとFISHを用いた胃癌における遺伝子増幅の準網羅的検索2014

    • Author(s)
      大井章史、田尻亮輔、中村律子、尾山武、池田博子、土橋洋
    • Organizer
      第103回日本病理学会総会
    • Place of Presentation
      ANAクラウンプラザホテル広島、広島
    • Year and Date
      2014-09-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] 腎癌における分泌型タンパクNell1/2の発現機能解析2014

    • Author(s)
      中村律子、尾山武、田尻良輔、大井章史
    • Organizer
      第103回日本病理学会総会
    • Place of Presentation
      広島国際会議場、広島
    • Year and Date
      2014-09-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] ヒト胃癌における癌関連遺伝子発現の腫瘍内不均一性を示す部分間における遺伝子発現の相違。2014

    • Author(s)
      尾山武、中村律子、田尻良輔、大井章史
    • Organizer
      第103回日本病理学会総会
    • Place of Presentation
      広島国際会議場、広島
    • Year and Date
      2014-04-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] ヒト胃癌における癌関連遺伝子発現の腫瘍内不均一性を示す部分間における遺伝子発現の相違2014

    • Author(s)
      尾山 武、中村 律子、田尻 亮輔、大井 章史
    • Organizer
      第103回日本病理学会総会
    • Place of Presentation
      広島国際会議場(広島)
    • Related Report
      2013 Research-status Report
  • [Presentation] Multiplex ligation-dependent probe amplification と FISH を用いた胃癌における遺伝子増幅の準網羅的検索2014

    • Author(s)
      大井 章史、田尻 亮輔、中村 律子、尾山 武、池田博子、土橋洋
    • Organizer
      第103回日本病理学会総会
    • Place of Presentation
      広島国際会議場(広島)
    • Related Report
      2013 Research-status Report
  • [Presentation] 腎癌における分泌型タンパク Nell 1/2 の発現機能解析2014

    • Author(s)
      中村 律子、尾山 武、田尻 亮輔、大井 章史
    • Organizer
      第103回日本病理学会総会
    • Place of Presentation
      広島国際会議場(広島)
    • Related Report
      2013 Research-status Report
  • [Presentation] HER2発現の腫瘍内ヘテロ不均一性を示す胃癌における遺伝子発現の網羅的解析2013

    • Author(s)
      尾山 武、中村 律子、田尻 亮輔、大井 章史
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2013 Research-status Report
  • [Presentation] FISHとMLPAを用いた胃癌におけるHER2遺伝子増幅の腫瘍内不均一性の検討2013

    • Author(s)
      大井 章史、田尻 亮輔、中村 律子、尾山 武、藤村 隆、土橋洋
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2013 Research-status Report
  • [Presentation] 腎癌における分泌型タンパク質Nell1/2の発現および機能解析2013

    • Author(s)
      中村 律子、尾山 武、田尻 亮輔、大井 章史
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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