Epigenetic dysregulation during development of HCC

• Project/Area Number: 23790775
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: The University of Tokyo
• Principal Investigator: NAGAE Genta 東京大学, 先端科学技術研究センター, 助教 (10587348)
• Research Collaborator: MIDORIKAWA Yutaka 日本大学, 医学部附属病院消化器外科, 助教 (10292905)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 肝臓学 / 肝臓癌 / エピジェネティクス / 肝癌 / メチル化

Research Abstract

To investigate the molecular changes during hepatocarcinogenesis, we performed integrative genomic and epigenomic analysis of HCC progressing in a nodule-in-nodule fashion. Whereas most aberrant DNA methylation was detected already in outer nodules, additional chromosomal changes were newly observed during the progression from outer nodules to inner nodules. Some HCC show methylation-dominant changes during progression conversely. These results may suggest stepwise accumulation of both genomic and epigenomic alteration in malignant progression of HCC.

Research Products

• [Journal Article] The role of NF-κB signaling in the maintenance of pluripotency of human induced pluripotent stem cells (2013)
  • Author(s): Takase O, Yoshikawa M, Idei M, Hirahashi J, Fujita T, Takato T, Isagawa T, Nagae G, Suemori H, Aburatani H, Hishikawa K
  • Journal Title: PLoS One Volume: 8(2) Issue: 2 Pages: e56399-e56399
  • DOI: 10.1371/journal.pone.0056399
  • Peer Reviewed
• [Journal Article] Generation of induced pluripotent stem cells from primary chronic myelogenous leukemia patient samples. (2012)
  • Author(s): Kumano K, Arai S, Hosoi M, Taoka K,Takayama N, Otsu M, Nagae G, Ueda K,Nakazaki K, Kamikubo Y, Eto K,Aburatani H, Nakauchi H, Kurokawa M.
  • Journal Title: Blood. Volume: 119(26) Pages: 6234-42
• [Journal Article] Loss of5-hydroxymethylcytosine is accompanied with malignant cellular transformation. (2012)
  • Author(s): Kudo Y, Tateishi K, Yamamoto K, Yamamoto S, Asaoka Y, Ijichi H, Nagae G, Yoshida H, Aburatani H, Koike K.
  • Journal Title: Cancer Sci. Volume: 103(4) Pages: 670-6
• [Journal Article] Whole-exome sequencing of human pancreatic cancers and characterization of genomic instability caused by MLH1 haploinsufficiency and complete deficiency. (2012)
  • Author(s): Wang L, Tsutsumi S, Kawaguchi T, Nagasaki K, Tatsuno K, Yamamoto S, Sang F, Sonoda K, Sugawara M, Saiura A, Hirono S, Yamaue H, Miki Y, Isomura M, Totoki Y, Nagae G, Isagawa T, Ueda H, Murayama-Hosokawa S, Shibata T, Sakamoto H, Kanai Y, Kaneda A, Noda T, Aburatani H.
  • Journal Title: Genome Res. Volume: 22(2) Pages: 208-19
• [Journal Article] 【次世代シークエンサー 目的 別アドバンストメソッド】(第 5 章)エピジェ ネティクス解析編 ChIP-seq 解析 (2012)
  • Author(s): 永江玄太
  • Journal Title: 細胞工学(0287-3796)別冊次世代シークエンサー目的別アドバンストメソッド Pages: 150-157
• [Journal Article] Generation of induced pluripotent stem cells from primary chronic myelogenous leukemia (2012)
  • Author(s): Keiki Kumano
  • Journal Title: BLOOD Volume: 119 Issue: 26 Pages: 6234-6242
  • DOI: 10.1182/blood-2011-07-367441
  • Peer Reviewed
• [Journal Article] Loss of 5-hydroxymethylcytosine is accompanied with malignant cellular transformation (2012)
  • Author(s): Kudo Y, Aburatani H, et al.
  • Journal Title: Cancer Science Volume: 103 Issue: 4 Pages: 670-676
  • DOI: 10.1111/j.1349-7006.2012.02213.x
  • Peer Reviewed
• [Journal Article] Whole-exome sequencing of human pancreatic cancers and characterization of genomic instability caused by MLH1 haploinsufficiency and complete deficiency (2012)
  • Author(s): Wang L, Tsutsumi S, Kawaguchi T,Nagasaki K, Tatsuno K, Yamamoto S, SangF, Sonoda K, Sugawara M, Saiura A,Hirono S, Yamaue H, Miki Y, Isomura M,Totoki Y, Nagae G, Isagawa T, Ueda H,Murayama-Hosokawa S, Shibata T,Sakamoto H, Kanai Y, Kaneda A, Noda T,Aburatani H
  • Journal Title: Genome Research Volume: 22(2) Issue: 2 Pages: 208-19
  • DOI: 10.1101/gr.123109.111
  • Peer Reviewed
• [Journal Article] Activation of Bmp2-Smad1 signal and its regulation by coordinated alteration of H3K27 trimethylation in Ras-induced senescence. (2011)
  • Author(s): Kaneda A, Fujita T, Anai M, Yamamoto S, Nagae G, Morikawa M, Tsuji S, Oshima M, Miyazono K, Aburatani H.
  • Journal Title: PLoS Genet. Volume: 7(11)
• [Journal Article] DNA methylation profiling of embryonic stem cell differentiation into the three germ layers. (2011)
  • Author(s): Isagawa T, Nagae G, Shiraki N, Fujita T, Sato N, Ishikawa S, Kume S, Aburatani H.
  • Journal Title: PLoS One. Volume: 6(10)
• [Journal Article] Classification of Epstein-Barr virus-positive gastric cancers by definition of DNA methylation epigenotypes. (2011)
  • Author(s): Matsusaka K, Kaneda A, Nagae G, Ushiku T, Kikuchi Y, Hino R, Uozaki H, Seto Y, Takada K, Aburatani H, Fukayama M.
  • Journal Title: Cancer Res. Volume: 71(23) Pages: 7187-97
• [Journal Article] Methylation screening of reciprocal genome-wide UPDs identifies novel human-specific imprinted genes. (2011)
  • Author(s): Nakabayashi K, Trujillo AM, Tayama C, Camprubi C, Yoshida W, Lapunzina P, Sanchez A, Soejima H, Aburatani H, Nagae G, Ogata T, Hata K, Monk D.
  • Journal Title: Hum Mol Genet. Volume: 20(16) Pages: 3188-97
• [Journal Article] Tissue-specific demethylation in CpG-poor promoters during cellular differentiation. (2011)
  • Author(s): Nagae G, Isagawa T, Shiraki N, Fujita T, Yamamoto S, Tsutsumi S, Nonaka A, Yoshiba S, Matsusaka K, Midorikawa Y, Ishikawa S, Soejima H, Fukayama M, Suemori H, Nakatsuji N, Kume S, Aburatani H.
  • Journal Title: Hum Mol Genet. Volume: 20(14) Pages: 2710-21
• [Journal Article] 肝細胞癌の遺伝的基盤肝細胞癌の統合的 ゲノム解析の現況 (2011)
  • Author(s): 永江玄太
  • Journal Title: The Liver Cancer Journal(1883-9347) Volume: 3巻1号 Pages: 34-39
• [Journal Article] Tissue-specific demethylation in CpG-poor promoters during cellular differentiation (2011)
  • Author(s): Nagae G, Isagawa T, Shiraki N, Fujita T, Yamamoto S, Tsutsumi S, Nonaka A,Yoshiba S, Matsusaka K, Midorikawa Y,Ishikawa S, Soejima H, Fukayama M,Suemori H, Nakatsuji N, Kume S,Aburatani H
  • Journal Title: Hum Mol Genetics Volume: 20(14) Issue: 14 Pages: 2710-21
  • DOI: 10.1093/hmg/ddr170
  • Peer Reviewed
• [Journal Article] Classification of Epstein-Barr virus-positive gastric cancers by definition of DNA methylation epigenotypes (2011)
  • Author(s): Matsusaka K, Kaneda A, Nagae G, Ushiku T, Kikuchi Y, Hino R, Uozaki H, Seto Y, Takada K, Aburatani H, Fukayama M.
  • Journal Title: Cancer Research Volume: 71(23) Pages: 7187-97
  • Peer Reviewed
• [Journal Article] DNA Methylation Profiling of Embryonic Stem Cell Differentiation into the Three Germ Layers (2011)
  • Author(s): Isagawa T, Nagae G, Shiraki N, Fujita T, Sato N, Ishikawa S, Kume S, Aburatani H
  • Journal Title: PLoS ONE Volume: 6(10) Issue: 10 Pages: e26052-e26052
  • DOI: 10.1371/journal.pone.0026052
  • Peer Reviewed
• [Journal Article] Methylation screening of reciprocal genome-wide UPDs identifies novel human-specific imprinted genes (2011)
  • Author(s): Nakabayashi K, Aburatani H, et al.
  • Journal Title: Hum Mol Genet Volume: 20 Issue: 16 Pages: 3188-97
  • DOI: 10.1093/hmg/ddr224
  • Peer Reviewed
• [Journal Article] Activation of Bmp2-Smad1 signal and its regulation by coordinated alteration of H3K27 trimethylation in Ras-induced senescence (2011)
  • Author(s): Kaneda A, Fujita T, Anai M, Yamamoto S,Nagae G, Morikawa M, Tsuji S, Oshima M,Miyazono K, Aburatani H
  • Journal Title: PLoS Genetics Volume: 7(11) Issue: 11 Pages: e1002359-e1002359
  • DOI: 10.1371/journal.pgen.1002359
  • Peer Reviewed
• [Presentation] 細胞分化過程におけるシトシン 修飾のダイナミクス (2012)
  • Author(s): 永江玄太
  • Organizer: ADVANS 研究会 2012
  • Place of Presentation: 東京
  • Year and Date: 2012-12-15
• [Presentation] Genome-wide profiling of promoter methylation identifies distinct subgroups in hepatocellular carcinoma, (2012)
  • Author(s): Nagae G, Midorikawa Y, Tatsuno K, TsujiS, Yamamoto S, Tsutsumi S, Ishikawa S,Aburatani H
  • Organizer: The 71th Japan Cancer Association Annual Meeting (InternationalSession)
  • Place of Presentation: Sapporo.
  • Year and Date: 2012-09-20
• [Presentation] Epigenetics (2012)
  • Author(s): Nagae G, Shiraki N, Kamio A, Fujita T,Kume S, Aburatani H.
  • Organizer: Cytosine methylation dynamics during hepatic differentiation Cold Spring Harbor Laboratory Meeting
  • Place of Presentation: Cold Spring Harbor, NY(USA).
  • Year and Date: 2012-09-12
• [Presentation] Genome-wide profiling of promoter methylation identifies distinct subgroups in hepatocellular carcinoma (2012)
  • Author(s): Nagae G, Midorikawa Y, Tatsuno K, Tsuji S, Yamamoto S, Tsutsumi S, Ishikawa S, Aburatani H
  • Organizer: 第6回日本エピジェネティクス研究会
  • Place of Presentation: 東京
  • Year and Date: 2012-05-12
• [Presentation] 組織分化過程における低 CpG プロモーターの脱メチル化 (2011)
  • Author(s): 永江玄太、砂河孝行、白木伸明、末盛博文、粂昭苑、油谷浩幸
  • Organizer: 第34回日本分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-13
• [Presentation] Genome-wide profiling of promoter methylation identifies distinct subgroups in hepatocellular carcinoma (2011)
  • Author(s): Nagae G, Midorikawa Y, Tatsuno K, Tsuji S, Yamamoto S, Tsutsumi S, Ishikawa S, Aburatani H
  • Organizer: The 70th Japan Cancer Association Annual Meeting (International Session)
  • Place of Presentation: Nagoya.
  • Year and Date: 2011-10-04
• [Presentation] High-resolution profiling of DNA methylation changes during in vitro cellular differentiation (2011)
  • Author(s): Nagae G, Isagawa T, Shiraki N, Suemori H, Kume S, Aburatani H
  • Organizer: The 9th International Workshop on Advanced Genomics
  • Place of Presentation: Tokyo.
  • Year and Date: 2011-07-12
• [Presentation] 組織分化過程における低 CpG プロモーターの脱メチル化 (2011)
  • Author(s): 永江玄太、砂河孝行、白木伸明、末盛博文、粂昭苑、油谷浩幸
  • Organizer: 第5回日本 エピジェネティクス研究会
  • Place of Presentation: 熊本
  • Year and Date: 2011-05-20
• [Presentation] Tissue-type specific hypomethylation in CpG-poor promoters during cellular differentiation (2011)
  • Author(s): Nagae G, Isagawa T, Shiraki N, Suemori H, Kume S, Aburatani H
  • Organizer: The 6th Asian Epigenomics Meeting
  • Place of Presentation: Kumamoto
  • Year and Date: 2011-05-18
• [Presentation] Tissue-type specific hypomethylation in CpG-poor promoters during cellular differentiation (2011)
  • Author(s): Nagae G, Isagawa T, Shiraki N, Suemori H, Kume S, Aburatani H
  • Organizer: The 6th Asian Epigenomics Meeting(招待講演)
  • Place of Presentation: 熊本
• [Presentation] ゲノムワイドなプロモーターメチル化解析による肝癌の分子生物学的層別化 (2011)
  • Author(s): 永江玄太, 緑川泰, 辰野健二, 辻真吾, 山本尚吾, 堤修一, 石川俊平, 油谷浩幸
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] 組織分化過程における低CpGプロモーターの脱メチル化 (2011)
  • Author(s): 永江玄太、砂河孝行、白木伸明、末盛博文、粂昭苑、油谷浩幸
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] Genome-wide profiling of promoter methylation identifies distinct subgroups in hepatocellular carcinoma
  • Author(s): Nagae G, Midorikawa Y, Tatsuno K, Tsuji S, Yamamoto S, Tsutsumi S, Ishikawa S, Aburatani H
  • Organizer: The 71th Japan Cancer Association Annual Meeting (International Session)
  • Place of Presentation: Sapporo
• [Presentation] Cytosine methylation dynamics during hepatic differentiation
  • Author(s): Nagae G, Shiraki N, Kamio A, Fujita T, Kume S, Aburatani H
  • Organizer: Cold Spring Harbor Laboratory Meeting, Epigenetics
  • Place of Presentation: Cold Spring Harbor (USA)
• [Presentation] 細胞分化過程におけるシトシン修飾のダイナミクス
  • Author(s): 永江玄太
  • Organizer: ADVANS研究会2012
  • Place of Presentation: 東京
  • Invited
• [Book] 細胞工学別冊 次世代シークエンサー 目的別アドバンストメソッド (2012)
  • Author(s): 永江玄太
  • Total Pages: 8
  • Publisher: 学研メディカル秀潤社
• [Remarks] 東京大学先端科学技術研究センターゲノムサイエンス分野
  • URL: http://www.genome.rcast.u-tokyo.ac.jp/
• [Remarks] 東京大学先端科学技術研究センター ゲノムサイエンス分野
  • URL: http://www.genome.rcast.u-tokyo.ac.jp/