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Identification of tumor suppressor genes in gastric cancers by genome-wide analysis of DNA methylation and its functional analysis

Research Project

Project/Area Number 17013090
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionNational Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East

Principal Investigator

USHIJIMA Toshikazu  National Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East, 発がん研究部, 部長 (90232818)

Co-Investigator(Kenkyū-buntansha) MORIGUCHI Kazuki  国立がんセンター(研究所及び東病院臨床開発センター), 発がん研究部, 研究員 (30294523)
ABE Masanobu  国立がんセンター(研究所及び東病院臨床開発センター), 発がん研究部, 研究員 (10392333)
YAMASHITA Sayoshi  国立がんセンター(研究所及び東病院臨床開発センター), 発がん研究部, 室長 (80321876)
WATANABE Naoko  国立がんセンター(研究所及び東病院臨床開発センター), 発がん研究部, 研究員 (80255364)
ASADA Kiyoshi  国立がんセンター(研究所及び東病院臨床開発センター), 発がん研究部, 主任研究官 (50311410)
Project Period (FY) 2005 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥41,800,000 (Direct Cost: ¥41,800,000)
Fiscal Year 2009: ¥8,300,000 (Direct Cost: ¥8,300,000)
Fiscal Year 2008: ¥8,300,000 (Direct Cost: ¥8,300,000)
Fiscal Year 2007: ¥8,300,000 (Direct Cost: ¥8,300,000)
Fiscal Year 2006: ¥8,300,000 (Direct Cost: ¥8,300,000)
Fiscal Year 2005: ¥8,600,000 (Direct Cost: ¥8,600,000)
Keywordsエピジェネティクス / 胃がん / DNAメチル化 / ゲノム / サイレンシング / DNAメチルヒ / ゲノム網羅的解析 / ユビジェネティクス / CpGアイランドメチル化形質
Research Abstract

Molecular mechanisms of methylation induction and its inducing factors are still unclear. We showed that the increased methylation of scattered CpG sites could lead to dense methylation of an entire CGI, and could methylate even genes with high expression. We also showed that specific genes were methylated in gastric mucosae with Helicobacter pylori (H.pylori) infection, and that low gene transcription is an important factor to determine the specificity. Using the Mongolian gerbil model, we showed that the types of inflammations are important for induction of aberrant DNA methylation.

Report

(6 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (58 results)

All 2010 2009 2008 2007 2006 2005

All Journal Article (32 results) (of which Peer Reviewed: 25 results) Presentation (26 results)

  • [Journal Article] Inflammatory processes triggered by H. pylori infection cause aberrant DNA methylation in gastric epithelial cells.2010

    • Author(s)
      Niwa T, Tsukamoto T, Toyoda T, Mori A, Tanaka H, Maekita T, Ichinose M, Tatematsu M, Ushijima T.
    • Journal Title

      Cancer Res 70

      Pages: 1430-1440

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Methylation Destiny : Moira Takes Account of Histones and RNA Polymerase II.2010

    • Author(s)
      Takeshima, H.
    • Journal Title

      Epigenetics 5

      Pages: 89-95

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The presence of a methylation fingerprint of Helicobacter pylori infection in human gastric mucosae.2009

    • Author(s)
      Nakajima T, Yamashita S, Maekita T, Niwa T, Nakazawa K, Ushijima T.
    • Journal Title

      Int J Cancer 124

      Pages: 905-910

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Persistence of a component of DNA methylation in gastric mucosae after Helicobacter pylori eradication.2009

    • Author(s)
      Nakajima T, Enomoto S, Yamashita S, Ando T, Nakanishi Y, Nakazawa K, Oda I, Gotoda T, Ushijima T.
    • Journal Title

      J Gastroenterol 45

      Pages: 37-44

    • NAID

      10027213841

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] DNA methylation of microRNA genes in gastric mucosae of gastric cancer patients: its possible involvement in the formation of epigenetic field defect.2009

    • Author(s)
      Ando T, Yoshida T, Enomoto S, Asada K, Tatematsu M, Ichinose M, Sugiyama T, Ushijima T.
    • Journal Title

      Int J Cancer 124

      Pages: 2367-2374

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] RUNX3 expression correlates with chief cell differentiation in human gastric cancers.2009

    • Author(s)
      Ogasawara N, Tsukamoto T, Mizoshita T, Inada KI, Ban H, Kondo S, Takasu S, Ushijima T, Ito K, ItoY, Ichinose M, Ogawa T, Joh T, Tatematsu M.
    • Journal Title

      Histol Histopathol 24

      Pages: 31-40

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Methylationsensitive representational difference analysis (MS-RDA).2009

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

      Methods Mol Biol 507

      Pages: 117-130

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Development of a novel output value for quantitative assessment in methylated DNA immunoprecipitation-CpG island microarray analysis.2009

    • Author(s)
      Yamashita, S.
    • Journal Title

      DNA Res 16

      Pages: 275-286

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The presence of RNA polymerase II, active or stalled, predicts epigenetic fate of promoter CpG islands.2009

    • Author(s)
      Takeshima, H.
    • Journal Title

      Genome Res 19

      Pages: 1974-1982

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The presence of a methylation fingerprint of Helicobacter pylori infection in human gastric mucosae.2009

    • Author(s)
      Nakajima, T.
    • Journal Title

      Int J Cancer 124

      Pages: 905-910

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] RUNX3 expression correlates with chief cell differentiation in human gastric cancers.2009

    • Author(s)
      Ogasawara, N.
    • Journal Title

      Histol Histopathol 24

      Pages: 31-40

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The presence of a methylation fingerprint of Helicobacter pylori infection in human gastric mucosae.2009

    • Author(s)
      Nakajima, T., Yamashita, S., Maekita, T., Niwa, T., Nakazawa, K., and Ushijima, T.
    • Journal Title

      Int J Cancer 124

      Pages: 905-910

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] RUNX3 expression correlates with chief cell differentiation in human gastric cancers.2009

    • Author(s)
      Ogasawara, N., Tsukamoto, T., Mizoshita, T., Inada, KI., Ban, H., Kondo, S., Takasu, S., Ushijima, T., Ito, K., Ito, Y., Ichinose, M., Ogawa, T., Joh, T., and Tatematsu, M.
    • Journal Title

      Histol Histopathol 24

      Pages: 31-40

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Larger numbers of silenced genes in cancer cell lines with increased de novo methylation of scattered CpG sites.2007

    • Author(s)
      Moriguchi K, Yamashita S, Tsujino Y, Tatematsu M, Ushijima T.
    • Journal Title

      Cancer Lett 249

      Pages: 178-187

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Epigenetic field for cancerization.2007

    • Author(s)
      Ushijima T.
    • Journal Title

      J Biochem Mol Biol 40

      Pages: 142-150

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Lack of association between CpG island methylator phenotype in human gastric cancers and methylation in their background non-cancerous gastric mucosae.2007

    • Author(s)
      Enomoto S, Maekita T, Tsukamoto T, Nakajima T, Nakazawa K, Tatematsu M, Ichinose M, Ushijima T.
    • Journal Title

      Cancer Sci 98

      Pages: 1853-1861

    • NAID

      10019996096

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cyclin D1 overexpression in N-methyl-N'-nitro-Nnitrosoguanidine- induced rat gastric adenocarcinomas.2007

    • Author(s)
      Takasu S, TsukamotoT, Ushijima T, Yamashita S, Ogasawara N, Ban H, Yanai T, Masegi T, Tatematsu M.
    • Journal Title

      Exp Toxicol Pathol 59

      Pages: 171-175

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Larger numbers of silenced genes in cancer cell lines withincreased de novomethvlation of scattered CnG sites2007

    • Author(s)
      Moriguchi, K., et. al.
    • Journal Title

      Cancer Letters 249

      Pages: 178-187

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epigenetic field for cancerization.2007

    • Author(s)
      Ushijima, T.
    • Journal Title

      Journal of Biochemistxy and Molecular Biology 40

      Pages: 142-150

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lack of association between CpG island methylator phenotype in human gastriccancers and methylation in their background non-cancerous gastric mucosae2007

    • Author(s)
      Enomoto, S., et. al.
    • Journal Title

      Cancer Science 98

      Pages: 1853-1861

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cyclin Dloverexpression in N-methyl-N'-nitro-N-nitrosoguanidine-inducedratastric adenocarcinomas.2007

    • Author(s)
      Takasu, S., et. al.
    • Journal Title

      Experimental and Toxicologic Pathology 59

      Pages: 171-175

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Larger numbers of silenced genes in cancer cell lines with increased de novo methylation of scattered CpG sites.2007

    • Author(s)
      Moriguchi, K., et al.
    • Journal Title

      Cancer Letters 249(2)

      Pages: 178-187

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Epigenetic field for cancerization.2007

    • Author(s)
      Ushijima, T.
    • Journal Title

      Journal of Biochemistry and Molecular Biology 40(2)

      Pages: 142-150

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2'-deoxycytidine treatment and oligonucleotide microarray.2006

    • Author(s)
      Yamashita S, Tsujino Y, Moriguchi K, Tatematsu M, Ushijima T.
    • Journal Title

      Cancer Sci 97

      Pages: 64-71

    • NAID

      10017103807

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] A specific CpG site demethylation in the human interleukin 2 gene promoter is an epigenetic memory.2006

    • Author(s)
      Murayama A, Sakura K, Nakama M, Yasuzawa-Tanaka K, Fujita E, Tateishi Y, Wang Y, Ushijima T, Baba T, Shibuya K, Shibuya A, Kawabe Y, Yanagisawa J.
    • Journal Title

      EMBO J 25

      Pages: 1081-1092

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genome-wide profiling of promoter methylation in human.2006

    • Author(s)
      Hatada I, Fukasawa M, Kimura M, Morita S, Yamada K, Yoshikawa T, Yamanaka S, Endo C, Sakurada A, Sato M, Kondo T, Horii A, Ushijima T, Sasaki H.
    • Journal Title

      Oncogene 25

      Pages: 3059-3064

    • NAID

      120000908395

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2'-deoxycytidine treatment and oligonucleotide microarray.2006

    • Author(s)
      Yamashita, S., et al.
    • Journal Title

      Cancer Science 97(1)

      Pages: 64-71

    • NAID

      10017103807

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Genome-wide profiling of promoter methylation in human.2006

    • Author(s)
      Hatada, I., et al.
    • Journal Title

      Oncogene 25(21)

      Pages: 3059-3064

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2'-deoxycytidine treatment and oligonucleotide microarray.2006

    • Author(s)
      Yamashita, S.他
    • Journal Title

      Cancer Sci. 97

      Pages: 64-71

    • NAID

      10017103807

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A specific CpG site demethylation in the human interleukin 2 gene promoter is an epigenetic memory.2006

    • Author(s)
      Murayama, A.他
    • Journal Title

      EMBO J. 25

      Pages: 1081-1092

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Decreased fidelity in replicating CpG methylation patterns in cancer cells.2005

    • Author(s)
      Ushijima T, Watanabe N, Shimizu K, Miyamoto K, Sugimura T, Kaneda A.
    • Journal Title

      Cancer Res 65

      Pages: 11-17

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Decreased fidelity in replicating CpG methylation patterns in cancer cells.2005

    • Author(s)
      Ushijima, T.他
    • Journal Title

      Cancer Res. 65

      Pages: 11-17

    • Related Report
      2005 Annual Research Report
  • [Presentation] Instructive induction of aberrant DNA methylation, and epigenomic analysis of its underlying mechanisms.2009

    • Author(s)
      Ushijima T.
    • Organizer
      第32回日本分子生物学会年会シンポジウム
    • Place of Presentation
      横浜
    • Year and Date
      2009-12-10
    • Related Report
      2009 Annual Research Report 2009 Final Research Report
  • [Presentation] Instructive induction of aberrant DNA methylation, and epigenomic analysis of its underlying mechanisms.2009

    • Author(s)
      Ushijima T.
    • Organizer
      Epigenetics 2009 Australian Scientific Meeting.
    • Place of Presentation
      Melbourne
    • Year and Date
      2009-12-02
    • Related Report
      2009 Annual Research Report 2009 Final Research Report
  • [Presentation] The presence of strong target gene specificity in induction of DNA methylation, and its mechanisms.2009

    • Author(s)
      Ushijima T.
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2009-10-03
    • Related Report
      2009 Annual Research Report 2009 Final Research Report
  • [Presentation] The presence of strong target gene specificity in induction of DNA methylation, and its mechanisms.2009

    • Author(s)
      Ushijima T.
    • Organizer
      Epigenetics in Development and Diseases Conference: 4th Asian Epigenomics Meeting.
    • Place of Presentation
      Singapore
    • Year and Date
      2009-08-25
    • Related Report
      2009 Final Research Report
  • [Presentation] The presence of strong target gene specificity in induction of DNA methylation, and its mechanisms.2009

    • Author(s)
      Ushijima, T.
    • Organizer
      Epigenetics in Development and Diseases Conference : 4th Asian Epigenomics Meeting.
    • Place of Presentation
      Singapore
    • Year and Date
      2009-08-25
    • Related Report
      2009 Annual Research Report
  • [Presentation] The presence of strong target gene specificity in induction of DNA methylation, and its mechanisms.2009

    • Author(s)
      Ushijima T.
    • Organizer
      18th Cancer Research Institute cancer symposium on "DNA and Histone Methylation in Cancer".
    • Place of Presentation
      Seoul
    • Year and Date
      2009-06-05
    • Related Report
      2009 Annual Research Report 2009 Final Research Report
  • [Presentation] Expression and methylation changes of APC 1A and 1B in gastric carcinogenesis.2008

    • Author(s)
      Hosoya K, Yamashita S, Ando T, Nakajima T, Nakanishi Y, Itoh F, Ushijima T.
    • Organizer
      67th JCA meeting.
    • Place of Presentation
      Nagoya
    • Year and Date
      2008-10-28
    • Related Report
      2009 Final Research Report
  • [Presentation] DNA methylation induction by Helicobacter pylori infection in human gastric mucosae and target gene specificity.2008

    • Author(s)
      Nakajima T, Yamashita S, Maekita T, Niwa T, Nakazawa K, Ushijima T.
    • Organizer
      67th JCA meeting.
    • Place of Presentation
      Nagoya
    • Year and Date
      2008-10-28
    • Related Report
      2009 Final Research Report
  • [Presentation] Expression and methylation changes of APC 1A and 1B in gastric carcinogenesis.2008

    • Author(s)
      Hosoya, K., Yamashita, S., Ando, T., Nakajima, T., Nakanishi, Y., Itoh, F., and Ushijima, T.
    • Organizer
      67^<th> JCA meeting
    • Place of Presentation
      Nagoya
    • Year and Date
      2008-10-28
    • Related Report
      2008 Annual Research Report
  • [Presentation] DNA methylation induction by Helicobacter pylori infection in human gastric mucosae and target gene specificity.2008

    • Author(s)
      Nakajima, T., Yamashita, S., Maekita, T., Niwa, T., Nakazawa, K., and Ushijima, T.
    • Organizer
      67^<th> JCA meeting
    • Place of Presentation
      Nagoya
    • Year and Date
      2008-10-28
    • Related Report
      2008 Annual Research Report
  • [Presentation] 神経芽腫の強力予後因子としてのDNAメチル化2007

    • Author(s)
      牛島 俊和
    • Organizer
      小児癌学会・小児血液学会シンポジウム
    • Place of Presentation
      宮城県仙台市仙台国際センター
    • Year and Date
      2007-12-15
    • Related Report
      2007 Annual Research Report
  • [Presentation] Epigenetic field defect for gastric cancers, and its use as a cancer riskmarker2007

    • Author(s)
      Ushijima, T.
    • Organizer
      The llth Annual Meeting of Taiwan Cooperative Oncology Group
    • Place of Presentation
      Taipei (Taiwan) Howard International House
    • Year and Date
      2007-12-02
    • Related Report
      2007 Annual Research Report
  • [Presentation] Epigenetic field for cancerization2007

    • Author(s)
      Ushijima, T.
    • Organizer
      11th German-Japan Cancer Research Workshop
    • Place of Presentation
      Kyoto (Japan) Kvoto Garden Palace
    • Year and Date
      2007-11-29
    • Related Report
      2007 Annual Research Report
  • [Presentation] エピジェネティックな発がんの場2007

    • Author(s)
      牛島 俊和
    • Organizer
      日本癌学会66回総会シンポジウム
    • Place of Presentation
      神奈川県横浜市パシフィコ横浜
    • Year and Date
      2007-10-05
    • Related Report
      2007 Annual Research Report
  • [Presentation] Epigenetics in Cancers and Polyclonal Disorders2007

    • Author(s)
      牛島 俊和
    • Organizer
      日本薬物動態学会ビジョンシンポジウム
    • Place of Presentation
      東京都港区共立薬科大学
    • Year and Date
      2007-07-19
    • Related Report
      2007 Annual Research Report
  • [Presentation] エピジェネティクスからみた多段階発がん2007

    • Author(s)
      牛島 俊和
    • Organizer
      日本エピジェネティクス研究会
    • Place of Presentation
      大阪府吹田市大阪大学コンベンションセンター
    • Year and Date
      2007-06-16
    • Related Report
      2007 Annual Research Report
  • [Presentation] Environment-epigenome interaction2007

    • Author(s)
      Ushijima, T.
    • Organizer
      Symposium by Asian Network of Epigenomics
    • Place of Presentation
      Osaka (Japan) Institute for Protein Research
    • Year and Date
      2007-06-14
    • Related Report
      2007 Annual Research Report
  • [Presentation] DNA methylation induction by Helicobacter pylori, and use as a cancer risk marker2007

    • Author(s)
      Ushijima, T.
    • Organizer
      The 19th Federation of Asian and Oceanian Biochemists and Molecular Biologists (FAOBMB) Conference
    • Place of Presentation
      Seoul(Korea)COEX Center
    • Year and Date
      2007-05-29
    • Related Report
      2007 Annual Research Report
  • [Presentation] Epigenetic field defect for gastric cancers2007

    • Author(s)
      Ushijima, T.
    • Organizer
      Gordon Research Conference
    • Place of Presentation
      Lucca (Italy) Il Ciocco
    • Year and Date
      2007-05-22
    • Related Report
      2007 Annual Research Report
  • [Presentation] DNA methylation as a marker for the past and future2007

    • Author(s)
      Ushijima, T.
    • Organizer
      The New Zealand Society for Oncology Conference
    • Place of Presentation
      Dunedin (NewZealand) Dunedin Centre
    • Year and Date
      2007-05-11
    • Related Report
      2007 Annual Research Report
  • [Presentation] Epigenetic field defect for gastric cancers.2007

    • Author(s)
      Ushijima T, Nakajima T, Enomoto S.
    • Organizer
      Gordon Research Conference.
    • Place of Presentation
      Il Ciocco
    • Related Report
      2009 Final Research Report
  • [Presentation] Epigenetic field defect for gastric cancers, and its use as a cancer risk marker.2007

    • Author(s)
      Ushijima T, Nakajima T.
    • Organizer
      The 11th Annual Meeting of Taiwan Cooperative Oncology Group.
    • Place of Presentation
      Taipei
    • Related Report
      2009 Final Research Report
  • [Presentation] A chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2'-deoxycytidine treatment and oligonucleotide microarray.2006

    • Author(s)
      Yamashita S, Tsujino Y, Moriguchi K, Tatematsu M, Ushijima T.
    • Organizer
      Annual Meeting of American Association for Cancer Research.
    • Place of Presentation
      Washington DC
    • Related Report
      2009 Final Research Report
  • [Presentation] エピジェネティックな異常の起源と加速Helicobacter pyloriによるDNAメチル化異常誘発とCpGアイランド特異性2006

    • Author(s)
      牛島俊和
    • Organizer
      日本癌学会65回総会シンポジウム
    • Related Report
      2009 Final Research Report
  • [Presentation] Helicobacter pyloriによる胃粘膜でのDNAメチル化異常誘発2006

    • Author(s)
      牛島俊和
    • Organizer
      日本分子生物学会2006フォーラム
    • Related Report
      2009 Final Research Report
  • [Presentation] ヘリコバクター・ピロリ感染による異常dnaメチル化の高度の蓄積2005

    • Author(s)
      前北隆雄、中沢和之、中島健、三原真美、清水靖仁、杉村隆、斉藤大三、一瀬雅夫、牛島俊和
    • Organizer
      第64回日本癌学会学術総会
    • Related Report
      2009 Final Research Report

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Published: 2005-04-01   Modified: 2018-03-28  

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