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Identification of novel tumor-suppressor genes by Outlier approach

Research Project

Project/Area Number 23710227
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Medical genome science
Research InstitutionNational Center of Neurology and Psychiatry

Principal Investigator

TAKESHIMA Hideyuki  独立行政法人国立がん研究センター, 研究所, 研究員 (40432497)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywordsエピジェネティクス / DNAメチル化 / がん抑制遺伝子 / サイレンシング / マイクロアレイ
Research Abstract

Aberrant DNA methylation of promoter CpG islands (CGIs) is deeply involved in human carcinogenesis. Although hundreds to thousands of genes are aberrantly methylated in cancer cells, the majority is methylated as a consequence of carcinogenesis, and it is difficult to identify tumor-suppressor genes (TSGs) from numerous methylated genes. In this study, we developed a novel method to identify TSGs based on our previous findings that genes with RNA polymerase II (Pol II) in normal cells are resistant to aberrant methylation induction and that known TSGs were methylated in cancers against this general rule. First, we identified 280 methylation-sensitive genes in human breast cancers. From these genes, 14 genes methylated against the general rule (outlier genes) were isolated by analyzing Pol II binding in normal cells. Among these genes, DZIP1 was a novel TSG, and FBN2 and HOXA5 were known TSGs. These results showed that TSGs can be efficiently identified by this approach.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (11 results)

All 2012 2011 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (7 results)

  • [Journal Article] Development of a novel approach, the epigenome-based outlier approach, to identify tumor-suppressor genes silenced by aberrant DNA methylation2012

    • Author(s)
      Kikuyama, M, Takeshima, H, Kinoshita, T, Okochi-Takada, E, Wakabayashi, M, Akashi-Tanaka, S, Ogawa, T, Seto, Y and Ushijima, T
    • Journal Title

      Cancer Lett.

      Volume: 322 Pages: 204-212

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Development of a novel approach, the epigenome-based outlier approach, to identify tumor-suppressor genes silenced by aberrant DNA methylation.2012

    • Author(s)
      Kikuyama, M, Takeshima, H, Kinoshita, T, Okochi-Takada, E, Wakabayashi, M, Akashi-Tanaka, S, Ogawa, T, Seto, Y and Ushijima, T.
    • Journal Title

      Cancer Letters

      Volume: 322 Issue: 2 Pages: 204-212

    • DOI

      10.1016/j.canlet.2012.03.016

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of genome architecture and epigenetic factors on susceptibility of promoter CpG islands to aberrant DNA methylation induction2011

    • Author(s)
      Takeshima, H, Yamashita, S, Shimazu, T and Ushijima, T
    • Journal Title

      Genomics

      Volume: 98 Pages: 182-188

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effects of genome architecture and epigenetic factors on susceptibility of promoter CpG islands to aberrant DNA methylation induction2011

    • Author(s)
      Takeshima H, Yamashita S, Shimazu T, Ushijima T.
    • Journal Title

      Genomics

      Volume: 98 Issue: 3 Pages: 182-8

    • DOI

      10.1016/j.ygeno.2011.06.003

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] The outlier approach discriminates drivers from passengers among genes methylated in cancer2012

    • Author(s)
      Kikuyama, M, Takeshima, H, Kinoshita, T, Okochi-Takada, E, Wakabayashi, M, Akashi-Tanaka, S, Ogawa, T, Seto, Y and Ushijima, T
    • Organizer
      AACR annual meeting 2012
    • Place of Presentation
      シカゴ(米国)
    • Year and Date
      2012-04-03
    • Related Report
      2013 Final Research Report
  • [Presentation] ゲノム構造及びエピジェネティック因子は独立してメチル化異常誘発に対する感受性に影響する2011

    • Author(s)
      竹島秀幸, 山下聡, 島津太一 and 牛島俊和
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-10-03
    • Related Report
      2013 Final Research Report 2011 Research-status Report
  • [Presentation] エピジェネティックに不活化された遺伝子の中からがん抑制遺伝子を選別する方法の開発2011

    • Author(s)
      菊山みずほ, 竹島秀幸, 大河内(髙田)江里子, 明石(田中)定子, 木下貴之, 小川利久, 瀬戸泰之 and 牛島俊和
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-10-03
    • Related Report
      2013 Final Research Report 2011 Research-status Report
  • [Presentation] 繰り返し配列LINE及びSINEはDNAメチル化異常誘発に対する感受性を与える2011

    • Author(s)
      竹島秀幸, 山下聡, 島津太一 and 牛島俊和
    • Organizer
      第5回日本エピジェネティクス研究会年会
    • Place of Presentation
      熊本
    • Year and Date
      2011-05-20
    • Related Report
      2013 Final Research Report 2011 Research-status Report
  • [Presentation] エピジェネティックに不活化された遺伝子の中からがん抑制遺伝子を選別する方法の開発2011

    • Author(s)
      菊山みずほ, 竹島秀幸, 大河内(髙田)江里子, 小川利久, 瀬戸泰之 and 牛島俊和
    • Organizer
      第5回日本エピジェネティクス研究会年会
    • Place of Presentation
      熊本
    • Year and Date
      2011-05-20
    • Related Report
      2013 Final Research Report
  • [Presentation] エピジェネティックに不活化された遺伝子の中からがん抑制遺伝子を選別する方法の開発.2011

    • Author(s)
      菊山みずほ, 竹島秀幸, 大河内(高田)江里子, 小川利久, 瀬戸泰之 and 牛島俊和.
    • Organizer
      第5回日本エピジェネティクス研究会年会
    • Place of Presentation
      熊本
    • Related Report
      2011 Research-status Report
  • [Presentation] The outlier approach discriminates drivers from passengers among genes methylated in cancers

    • Author(s)
      Kikuyama, M, Takeshima, H, Kinoshita, T, Okochi-Takada, E, Wakabayashi, M, Akashi-Tanaka, S, Ogawa, T, Seto, Y and Ushijima, T
    • Organizer
      AACR annual meeting 2012
    • Place of Presentation
      アメリカ・シカゴ
    • Related Report
      2012 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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