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2015 Fiscal Year Annual Research Report

MLPAとFISHを用いたヒト固形癌における遺伝子増幅の網羅的研究

Research Project

Project/Area Number 25460452
Research InstitutionKanazawa University

Principal Investigator

大井 章史  金沢大学, 医学系, 教授 (50160411)

Project Period (FY) 2013-04-01 – 2016-03-31
Keywords遺伝子増幅 / MLPA / FISH / 胃癌 / 受容体チロシンキナーゼ
Outline of Annual Research Achievements

The prognosis of patients with gastric carcinomas at an advanced stage still remains dismal and therefore novel therapeutic modalities are urgently needed. The aim of the present study was to determine the amplification status of 26 genes, which are frequently amplified in solid cancers, in advanced gastric cancers.
A total of 93 formalin-fixed and paraffin-embedded advanced gastric cancer tissues were examined by multiple ligation-dependent probe amplification (MLPA), and 32 cases with ‘gain’ or ‘amplified’ status of 16 genes were further examined for the respective gene amplification by fluorescence in situ hybridization (FISH). The frequencies of gene amplifications in advanced gastric cancers as assessed by these combined methods were as follows: ERBB2 (13 cases, 14.0%), FGFR2 (7 cases, 7.5%), MYC (7 cases, 7.5%), TOP2A (7 cases, 7.5%), MET (4 cases, 4.3%), MDM2 (4 cases, 4.3%), CCND1 (3 cases, 3.2%), FGF10 (2 cases, 3.2%), and EGFR (one case, 1.1%). Amplification of the RTK genes occurred in a mutually exclusive manner except for one tumor in which ERBB2 and FGFR2 were both amplified but in different cancer cells. Thus if a common tyrosine kinase inhibitor to the four RTKs were available, 24 of 93 (25.8%) cases of advanced gastric cancer would potentially be susceptible to that agent.
In conclusion, combination of MLPA and FISH analysis is a feasible approach for obtaining the semi-comprehensive genetic information that is necessary for personalized molecular targeted therapy.

  • Research Products

    (8 results)

All 2015

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Acknowledgement Compliant: 4 results) Presentation (3 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)
      Akishi Ooi, Takeru Oyama, Ritsuko Nakamura, Ryousuke Tajiri Hiroko Ikeda, Yukio Fushida, Hiroyuki Nakamura, and Yoh Dobashi.
    • Journal Title

      Mod Pathol

      Volume: 28 Pages: 861-871

    • DOI

      10.1038/modpathol.2015.33. Epub 2015 Mar 6.

    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Expression and regulatory effects on cancer cell behavior of NELL1 and NELL2 in human renal cell carcinoma2015

    • Author(s)
      Nakamura R, Oyama T, Tajiri R, Mizokami A, Namiki, M, Nakamoto M, Ooi A
    • Journal Title

      Cancer Sci

      Volume: 106 Pages: 656-664

    • DOI

      10.1111/cas.12649. Epub 2015 Mar 26.

    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Diverse involvement of isoforms and gene aberrations of Akt in human lung carcinomas.2015

    • Author(s)
      Yoh Dobashi, Hiroyoshi Tsubochi, Hirochika Matsubara, Jun Inoue, Johji Inazawa, Shunsuke Endo and Akishi Ooi.
    • Journal Title

      Cancer Sci

      Volume: 106 Pages: 772-81

    • DOI

      10.1111/cas.12669. Epub 2015 May 8.

    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Overexpression and gene amplification of both ERBB2 and EGFR in an esophageal squamous cell carcinoma revealed by fluorescence in situ hybridization, multiplex ligation-dependent probe amplification and immunohistochemistry.2015

    • Author(s)
      Takeru Oyama, Koichi Okamoto、 Ritsuko Nakamura, Ryosuke Tajiri, Hiroko Ikeda, Itasu Ninomiya , Akishi Ooi
    • Journal Title

      Pathol Int

      Volume: 65 Pages: 608-613

    • DOI

      10.1111/pin.12344. Epub 2015 Aug 28.

    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Co-active receptor tyrosine kinases mitigate the effect of FGFR inhibitors in FGFR1-amplified lung cancers with low FGFR1 protein expression2015

    • Author(s)
      Hiromichi Ebi, Hiroshi Kotani, Hidenori Kitai, Shigeki Nanjo, Kenji Kita, Seiji Yano, Akishi Ooi, Tiffany Huynh, Mari Mino-Kenudson, and Anthony C. Faber
    • Journal Title

      Oncogene

      Volume: 未定 Pages: 未定

    • DOI

      10.1038/onc.2015.426

    • Peer Reviewed
  • [Presentation] 1.MLPAとFISHを用いた、進行胃癌の遺伝子増幅の準網羅的検索2015

    • Author(s)
      大井章史、尾山武、中村律子、田尻亮輔。池田博子、土橋洋
    • Organizer
      第104回日本病理学会総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2015-04-30 – 2015-05-02
  • [Presentation] 2.アレイCGH法を用いたヒト胃癌に対するゲノムコピー数異常の網羅的解析2015

    • Author(s)
      尾山武、中村律子、田尻亮輔、大井章史
    • Organizer
      第104回日本病理学会総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2015-04-30 – 2015-05-02
  • [Presentation] 3.膀胱尿路上皮癌におけるFISH法を用いたCCND1およびMDM2遺伝子増幅の検索2015

    • Author(s)
      田尻亮輔、中村律子、尾山武、大井章史
    • Organizer
      第104回日本病理学会総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2015-04-30 – 2015-05-02

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Published: 2017-01-06  

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