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

2009 Fiscal Year Final Research Report

• Project/Area Number: 17013090
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: National 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
• Keywords: エピジェネティクス

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.

Research Products

• [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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Epigenetic field for cancerization. (2007)
  • Author(s): Ushijima T.
  • Journal Title: J Biochem Mol Biol 40 Pages: 142-150
  • 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
  • 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
  • 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, Tsujino Y, Moriguchi K, Tatematsu M, Ushijima T.
  • Journal Title: Cancer Sci 97 Pages: 64-71
  • 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
  • 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
  • Peer Reviewed
• [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
  • Peer Reviewed
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
  • Year and Date: 20071200
• [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
  • Year and Date: 20070500
• [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
  • Year and Date: 20061200
• [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
  • Year and Date: 20060900
• [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
  • Year and Date: 20060400
• [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
  • Year and Date: 20050900