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Analysis of gene amplifications of CCND1, CCNE1, and CDK6 in gastric cancers.

Research Project

Project/Area Number 16K08686
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Human pathology
Research InstitutionKanazawa University

Principal Investigator

Ooi Akishi  金沢大学, 医学系, 教授 (50160411)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Keywords胃癌 / 乳癌 / 遺伝子増幅 / MLPA / FISH / gene amplification / breast cancer / サイクリン / サイクリン依存性キナーゼ
Outline of Final Research Achievements

In solid cancers amplified genes are potential targets of molecular therapies. In this study the 16 genes and 22 genes reportedly amplified in gastric and mammary cancers were examined by multiplex ligation-dependent probe amplification and fluorescence in situ hybridization. In gastric cancers amplification of G1-S regulatory genes (CCNE1, CCND1and CDK6) were co-amplified with ERBB2, EGFR and/or KRAS in single cancer nuclei. In breast cancers The frequencies of the amplification of four regions containing known driver oncogenes were as follows: 8p11 (ZNF703, FGFR1, ADAM9 and IKBKB), 8q24 (MYC), 11q13 (CCND1, C11ORF30), and 17q11-21 (CPD, MED1, ERBB2, CDC6, TOP2A, MAPT) exhibited amplification in 9.6%, 9.6%, 12.4%, and 12.1% of the tumors, respectively. Co-localization of the amplicon on 8p11 and the amplicon on 11q13 in single cells was frequently observed. Precise and feasible analysis of gene amplification status can be obtained using a combination of MLPA and FISH.

Academic Significance and Societal Importance of the Research Achievements

固形癌において増幅遺伝子はしばしば分子標的の対象となる。本研究では胃癌、乳癌において標的候補遺伝子の出現頻度と分布を明らかし、創薬開発に貢献できた。また、分子標的療法を考えるとき、複数の遺伝子増幅が単一腫瘍細胞でおこっていることを念頭に入れることを喚起した。さらに、multiplex ligation-dependent probe amplificartion は比較的安価で網羅的に遺伝子増幅を知る手段であること、一方、fluorescence in situ hybridization は組織切片に適用することによって癌の’進化’の過程を終える手段であることを証明できた。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (7 results)

All 2019 2018 2017 2016

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

  • [Journal Article] Amplicons in breast cancers analyzed by multiplex ligation-dependent probe amplification and fluorescence in situ hybridization.2019

    • Author(s)
      Ooi A, Inokuchi M, Horike S, Kawashima H, Ishikawa S, Ikeda H, Nakamura R, Oyama T, Dobashi Y
    • Journal Title

      Hum Pathol.

      Volume: 85: Pages: 33-43

    • DOI

      10.1016/j.humpath.2018.10.017

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Detection of CCND1 gene copy number variations using multiplex ligation-dependent probe amplification and fluorescence in situ hybridization Methods.2018

    • Author(s)
      Ooi A and Oyama T
    • Journal Title

      Methods Mol Biol

      Volume: 1726 Pages: 101-109

    • DOI

      10.1007/978-1-4939-7565-5_10

    • NAID

      120006454998

    • ISBN
      9781493975648, 9781493975655
    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Gene amplification of CCNE1 CCND1, and CDK6 in gastric cancers detected by multiplex ligation-dependent probe amplification and fluorescence in situ hybridization。2017

    • Author(s)
      Ooi A et al.
    • Journal Title

      Hum Pathol

      Volume: 61 Pages: 58-67

    • DOI

      10.1016/j.humpath.2016.10.025

    • NAID

      120006226784

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Amplicons in breast cancers analyzed by multiplex ligation-dependent probe amplification and fluorescence in situ hybridization.2018

    • Author(s)
      大井章史、井口雅史、中村律子、尾山武、土橋洋
    • Organizer
      77th Annual Meeting of the Japanese Cancer Association.
    • Related Report
      2018 Annual Research Report
  • [Presentation] Gene amplification of CCNE1, CCND1 and CDK6 in gastric cancers2016

    • Author(s)
      Ooi A et al.
    • Organizer
      第75回日本癌学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] Gene amplification of CCNE1, CCND1 and CDK6 in gastric cancers2016

    • Author(s)
      Akishi Ooi
    • Organizer
      第105回日本病理学会
    • Place of Presentation
      仙台国際センター
    • Year and Date
      2016-05-14
    • Related Report
      2016 Research-status Report
  • [Book] ある病理医の絵日記2019

    • Author(s)
      大井章史
    • Total Pages
      74
    • Publisher
      田中昌文堂
    • Related Report
      2018 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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