The search for DNA methylation-based biomarkers in cancer

• Project/Area Number: 21590425
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Tohoku University
• Principal Investigator: FUKUSHIGE Shinichi 東北大学, 大学院・医学系研究科, 准教授 (90192723)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 腫瘍 / 遺伝子 / 発現制御 / 転写抑制 / メチルCpG結合蛋白 / エピジェネティクス / MeTA / マイクロアレイ / 遺伝子発現マイクロアレイ

Research Abstract

We have developed a novel method called"microarray coupled with methyl-CpG targeted transcriptional activation" (MeTA-array for short), which is useful in identifying hypermethylation-mediated silenced genes in cancer. The majority of genes identified by this method had more stringent criteria of CpG islands at the promoter region at high frequency. We have applied MeTA-array to pancreatic cancer cells and identified several genes hypermethylated in primary pancreatic cancers in a tumor-specific manner. These genes should be useful as candidates for tumor-specific biomarkers.

Research Products

• [Journal Article] Road to early detection of pancreatic cancer : Attempts to utilize epigenetic biomarkers (2012)
  • Author(s): Fukushige S, Horii A.
  • Journal Title: Cancer Lett Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] DCK is frequently inactivated in acquired gemcitabine-resistant human cancer cells. Biochem. Biophys (2012)
  • Author(s): Saiki Y, Yoshino Y, Fujimura H, Manabe T, Kudo Y, Shimada M, Mano N, Nakano T, Lee Y, Shimizu S, Oba S, Fujiwara S, Shimizu H, Chen N, Nezhad ZK, Jin G, Fukushige S, Sunamura M, Ishida M, Motoi F, Egawa S, Unno M, Horii A.
  • Journal Title: Res. Commun Volume: 421巻 Pages: 98-104
  • Peer Reviewed
• [Journal Article] Road to early detection of pancreatic cancer : Attempts to utilize epigenetic biomarkers (2012)
  • Author(s): Shinichi Fukushige
  • Journal Title: Cancer Lett Volume: (未定)(in press) Issue: 2 Pages: 231-237
  • DOI: 10.1016/j.canlet.2012.03.022
  • Peer Reviewed
• [Journal Article] DCK is frequently inactivated in acquired gemcitabine-resistant human cancer cells (2012)
  • Author(s): Yuriko Saiki
  • Journal Title: Biochemical and Biophysical Research Communications Volume: (in press) Issue: 1 Pages: 98-104
  • DOI: 10.1016/j.bbrc.2012.03.122
  • Peer Reviewed
• [Journal Article] Identification of epigenetically silenced genes in human pancreatic cancer by a novel method"microarray coupled with methyl-CpG targeted transcriptional activation" (MeTA-array) (2011)
  • Author(s): Shimizu H, Horii A, Sunamura M, Motoi F, Egawa S, Unno M, Fukushige S
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 411巻 Pages: 162-167
  • Peer Reviewed
• [Journal Article] Microarray coupled with methyl-CpG targeted transcriptional activation (MeTA-array)identifies hypermethylated genes containing the stringent criteria of CpG islands at high frequency (2011)
  • Author(s): Sato Y, Horii A, Fukushige S
  • Journal Title: Epigenetics Volume: 6巻 Pages: 752-759
  • Peer Reviewed
• [Journal Article] Microarray coupled with methyl-CpG targeted transcriptional activation (MeTA-array) identifies hypermethylated genes containing the stringent criteria of CpG islands at high frequency (2011)
  • Author(s): Yuko Sato
  • Journal Title: Epigenetics Volume: 6 Issue: 6 Pages: 752-759
  • DOI: 10.4161/epi.6.6.15906
  • Peer Reviewed
• [Journal Article] Identification of epigenetically silenced genes in human pancreatic cancer by a novel method "microarray coupled with methyl-CpG targeted transcriptional activation" (MeTA-array) (2011)
  • Author(s): Hideyuki Shimizu
  • Journal Title: Biochem Biophys Res Commun Volume: 411 Issue: 1 Pages: 162-167
  • DOI: 10.1016/j.bbrc.2011.06.121
  • Peer Reviewed
• [Presentation] メチルCpG配列を標的とする転写活性化とマイクロアレイの組み合わせはヒトがんにおける低メチル化遺伝子の同定を可能にする (2011)
  • Author(s): 福重真一、陳娜、堀井明
  • 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
• [Presentation] 大腸癌における新規癌抑制遺伝子NDRG2のエピジェネティックな発癌制御機構 (2011)
  • Author(s): 山村明寛、堀井明、三浦康、阿部佳子、内藤剛、小川仁、矢崎伸樹、羽根田祥、渡辺和宏、大沼忍、佐瀬友彦、鈴木秀幸、斉木由利子、福重真一、柴田近、佐々木巌
  • Organizer: 第74回大腸癌研究会
  • Place of Presentation: 福岡
  • Year and Date: 2011-01-21
• [Presentation] 大腸癌における新規癌抑制遺伝子NDRG2のエピジェネティックな発癌制御機構 (2011)
  • Author(s): 山村明寛
  • Organizer: 第74回 大腸癌研究会
  • Place of Presentation: 福岡
  • Year and Date: 2011-01-21
• [Presentation] S100A4 regulates tumor growth, motility, and invasion in pancreatic cancer (2011)
  • Author(s): Sekine H, Tabata T, Tsukamoto N, Chen N, Sato K, Umetsu Y, Nakamura K, Kim G, Yamamura A, Yoshino Y, Fukushige S, Sunamura M, Horii A.
  • Organizer: 60th Annual Meeting of the American Society of Human Genetics
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2011-01-03
• [Presentation] 癌抑制遺伝子NDRG2のエピジェネティックサイレンシングは消化器発癌を進行させる (2010)
  • Author(s): 山村明寛、三浦康、阿部佳子、福重真一、斉木由利子、木内誠、安藤敏典、唐澤秀明、金子直征、佐瀬友彦、柴田近、佐々木巌、堀井明
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-23
• [Presentation] 癌抑制遺伝子NDRG2のエピジェネティックサイレンシングは消化器発癌を進行させる (2010)
  • Author(s): 山村明寛
  • Organizer: 第69回 日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-23
• [Presentation] ヒトがんにおいて各メチルCpG結合ドメインは異なるメチル化遺伝子を標的とする能力をもつ (2010)
  • Author(s): 福重真一、堀井明
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-22
• [Presentation] ヒトがんにおいて各メチルCpG結合ドメインは異なるメチル化遺伝子を標的とする能力をもっ (2010)
  • Author(s): 福重真一
  • Organizer: 第69回 日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-22
• [Presentation] メチル化で発現抑制された遺伝子を特定する新規の方法「MeTA」の膵癌解析への応用 (2010)
  • Author(s): 清水秀幸、福重真一、堀井明
  • Organizer: 第99回日本病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 2010-04-29
• [Presentation] S100A4 regulates tumor growth, motility, and invasion in pancreatic cancer (2010)
  • Author(s): Sekine H, Tabata T, Tsukamoto N, Yamamura A, Abe K, Yoshino Y, Sato K, Chen N, Umetsu Y, Sato D, Gu Z, Fukushige S, Shima K, Motoi F, Egawa S, Sunamura M, Horii A.
  • Organizer: 101st American Association for Cancer Research Annual Meeting
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2010-04-21
• [Presentation] Expression of the N-myc downstream-regulated gene 2 (NDRG2)is frequently suppressed by promoter hypermethylation in human gastrointestinal and pancreatic cancers (2010)
  • Author(s): Yamamura A, Miura K, Karasawa H, Abe K, Mizuguchi Y, Jin G, Gu Z, Fukushige S, Kaneko N, Kinouchi M, Ando T, Yazaki N, Tanaka N, Sase T, Shibata C, Sasaki I, Horii A.
  • Organizer: 101st American Association for Cancer Research Annual Meeting
  • Place of Presentation: Washington DC, USA.
  • Year and Date: 2010-04-21
• [Presentation] Identification of novel targets for aberrant methylation in pancreatic cancer by a newly developed method"methyl-CpG targeted transcriptional activation (MeTA) (2010)
  • Author(s): Fukushige S, Shimizu H, Sato Y, Horii A.
  • Organizer: 101st American Association for Cancer Research Annual Meeting
  • Place of Presentation: Washington DC, USA.
  • Year and Date: 2010-04-18
• [Presentation] 癌抑制遺伝子NDRG2のエピジェネティックサイレンシングは消化器発癌を進行させる (2010)
  • Author(s): 山村明寛、三浦康、木内誠、安藤敏典、矢崎伸樹、田中直樹、唐澤秀明、佐瀬友彦、木村俊一、福重真一、Zhaodi Gu、嶋健太郎、柴田近、堀井明、佐々木巌
  • Organizer: 第110回日本外科学会定期学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-04-08
• [Presentation] メチルCpG配列を標的とする転写再活性化は、高度DNAメチル化で転写抑制された遺伝子の高感度かつ高精度な同定を可能にする (2009)
  • Author(s): 佐藤裕子、堀井明、福重真一
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-02
• [Presentation] メチルCpG配列を標的とする転写再活性化は、高度DNAメチル化で転写抑制された遺伝子の高感度かつ高精度な同定を可能にする (2009)
  • Author(s): 佐藤裕子
  • Organizer: 第68回 日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-02
• [Presentation] メチルCpG配列を標的とする転写再活性化による膵がんにおいてエピジェネティックに転写抑制された遺伝子の同定 (2009)
  • Author(s): 福重真一、堀井明
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01
• [Presentation] S100A4は膵癌細胞の増殖と浸潤を制御する (2009)
  • Author(s): 関根均、塚本信和、田畑孝洋、吉野優樹、梅津有紀子、Gu Zhaodi、佐藤大亮、嶋健太郎、福重真一、元井冬彦、江川新一、砂村眞琴、堀井明
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01
• [Presentation] 消化器癌においてNDRG2はプロモーターのメチル化によって発現抑制される (2009)
  • Author(s): 山村明寛、三浦康、木内誠、安藤敏典、矢崎伸樹、田中直樹、唐澤秀明、佐瀬友彦、福重真一、Zhaodi Gu、柴田近、佐々木巌、堀井明
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01
• [Presentation] メチルCpG配列を標的とする転写再活性化による膵がんにおいてテピジェネティックに転写抑制された遺伝子の同定 (2009)
  • Author(s): 福重真一
  • Organizer: 第68回 日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01
• [Presentation] S100A4は膵癌細胞の増殖と浸潤を制御する (2009)
  • Author(s): 関根均
  • Organizer: 第68回 日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01
• [Presentation] 消化器癌においてNDRG2はプロモーターのメチル化によって発現抑制される (2009)
  • Author(s): 山村明寛
  • Organizer: 第68回 日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01
• [Remarks]
  • URL: http://www.med.tohoku.ac.jp/~molpath/
• [Remarks]
  • URL: http://www.med.tohoku.ac.jp/~molpath/
• [Remarks]
  • URL: http://www.med.tohoku.ac.jp/~molpath/
• [Remarks]
  • URL: http://www.med.tohoku.ac.jp/~molpath/