Mechanisms of genetic alterations during the process of liver cancer development.

• Project/Area Number: 20590774
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kyoto University
• Principal Investigator: MARUSAWA Hiroyuki Kyoto University, 医学研究科, 講師 (80324630)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: AID / 肝癌 / 遺伝子変異 / APOBEC2 / 炎症 / p53

Research Abstract

Tumorigenesis is a multistep process in which the accumulation of genetic alterations drives the transformation of normal cells into malignant derivatives. Activation-induced cytidine deaminase (AID) contributes to immune system diversity by inducing somatic hypermutations and class-switch recombinations of human immunoglobulin genes. The mutagenic activity of AID, however, can also induce genetic changes including somatic mutations and submicroscopic chromosomal deletions in various gene loci in hepatocytes and gastric epithelial cells and may lead to the development of cancer.

Research Products

• [Journal Article] Excessive activity of APOBEC2 contributes to liver and lung tumorigenesis. (2011)
  • Author(s): Okuyama S, Marusawa H, Matsumoto T, Ueda Y, Matsumoto Y, Endo Y, Takai A, Chiba T.
  • Journal Title: Int J Cancer in press
  • Peer Reviewed
• [Journal Article] Excessive activity of APOBEC2 contributes to liver and lung tumorigenesis. (2011)
  • Author(s): Okuyama S, Marusawa H, Matsumoto T, Ueda Y, Matsumoto Y, Endo Y, Takai A, Chiba T.
  • Journal Title: Int J Cancer Volume: (Epub ahead of print (印刷中))
  • Peer Reviewed
• [Journal Article] Upregulation of activation-induced cytidine deaminase causes genetic aberrations at the CDKN2b-CDKN2a in gastric cancer. (2010)
  • Author(s): Matsumoto Y, Marusawa H, Kinoshita K, Niwa Y, Sakai Y, Chiba T.
  • Journal Title: Gastroenterology 139 Pages: 1984-94
  • NAID: 120002696051
  • Peer Reviewed
• [Journal Article] Helicobacter pylori-induced activation-induced cytidine deaminase expression and carcinogenesis. (2010)
  • Author(s): Marusawa H, Chiba T.
  • Journal Title: Curr Opin Immunol 22 Pages: 442-7
  • NAID: 120002511343
  • Peer Reviewed
• [Journal Article] Upregulation of activation-induced cytidine deaminase causes genetic aberrations at the CDKN2b-CDKN2a in gastric cancer. (2010)
  • Author(s): Matsumoto Y, Marusawa H, Kinoshita K, Niwa Y, Sakai Y, Chiba T.
  • Journal Title: Gastroenterology Volume: 139 Pages: 1984-1994
  • NAID: 120002696051
  • Peer Reviewed
• [Journal Article] Helicobacter pylori-induced activation-induced cytidine deaminase expression and carcinogenesis. (2010)
  • Author(s): Marusawa H, Chiba T.
  • Journal Title: Curr Opin Immunol Volume: 22 Pages: 442-447
  • NAID: 120002511343
  • Peer Reviewed
• [Journal Article] A novel mouse model of hepatocarcinogenesis triggered by AID causing deleterious p53 mutations. (2009)
  • Author(s): Takai A, Toyoshima T, Uemura M, Kitawaki Y, Marusawa H, Hiai H, Yamada S, Okazaki IM, Honjo T, Chiba T, Kinoshita K.
  • Journal Title: Oncogene 28 Pages: 469-478
  • Peer Reviewed
• [Journal Article] Attenuation of proteolysis-mediated cyclin E regulation by alternatively spliced Parkin in human colorectal cancers. (2009)
  • Author(s): Ikeuchi K, Marusawa H, Fujiwara M, Matsumoto Y, Endo Y, Watanabe T, Iwai A, Sakai Y, Takahashi R, Chiba T.
  • Journal Title: Int J Cancer 125 Pages: 2029-2035
  • Peer Reviewed
• [Journal Article] A novel mechanism for inflammation-associated carcinogenesis ; an important role of activation-induced cytidine deaminase (AID) in mutation induction. (2009)
  • Author(s): Chiba T, Marusawa H.
  • Journal Title: J Mol Med 87 Pages: 1023-1027
  • Peer Reviewed
• [Journal Article] A novel mouse model of hepatocarcinogenesis triggered by AID causing deleterious p53 mutations. (2009)
  • Author(s): Takai A, et al.
  • Journal Title: Oncogene 28 Pages: 469-478
  • Peer Reviewed
• [Journal Article] A novel mechanism for inflammation-associated carcinogenesis ; an important role of activation-induced cytidine deaminase (AID) in mutation induction. (2009)
  • Author(s): Chiba T Marusawa H.
  • Journal Title: J Mol Med 87 Pages: 1023-1027
  • Peer Reviewed
• [Journal Article] Organ-specific profiles of genetic changes in cancers caused by activation-induced cytidine deaminase expression. (2008)
  • Author(s): Morisawa T, Marusawa H, Ueda Y, Iwai A, Okazaki IM, Honjo T, Chiba T.
  • Journal Title: Int J Cancer 123 Pages: 2735-2740
  • Peer Reviewed
• [Journal Article] Activation-induced cytidine deaminase links between inflammation and the development of colitis-associated colorectal cancers. (2008)
  • Author(s): Endo Y, Marusawa H, Kou T, Nakase H, Fujii S, Fujimori T, Kinoshita K, Honjo T, Chiba T.
  • Journal Title: Gastroenterology 135 Pages: 889-898
  • Peer Reviewed
• [Journal Article] Parkin as a tumor suppressor gene for hepatocellular carcinoma. (2008)
  • Author(s): Fujiwara M, Marusawa H, Wang HQ, Iwai A, Ikeuchi K, Imai Y, Kataoka A, Nukina N, Takahashi R, Chiba T.
  • Journal Title: Oncogene 27 Pages: 6002-6011
  • Peer Reviewed
• [Journal Article] Aberrant AID expression and human cancer development. (2008)
  • Author(s): Marusawa H
  • Journal Title: Int J Biochem Cell Biol 40 Pages: 1399-1402
  • Peer Reviewed
• [Journal Article] Activation-induced cytidine deaminase links bile duct inflammation to human cholangiocarcinoma. (2008)
  • Author(s): Komori J, Marusawa H, Machimoto T, Endo Y, Kinoshita K, Kou T, Haga H, Ikai I, Uemoto S, Chiba T.
  • Journal Title: Hepatology 47 Pages: 888-896
  • Peer Reviewed
• [Journal Article] Aberrant AID expression and human cancer development. (2008)
  • Author(s): Marusawa H
  • Journal Title: Int J Biochem Cell Biol. 40 Pages: 1399-1404
  • Peer Reviewed
• [Journal Article] Organ-specific profiles of genetic changes in cancers caused by AID expression. (2008)
  • Author(s): Morisawa T, Marusawa H, et al.
  • Journal Title: Int J Cancer. 123 Pages: 2735-2740
  • Peer Reviewed
• [Presentation] AIDによる発癌関連遺伝子への変異生成と炎症発癌 (2010)
  • Author(s): 丸澤宏之
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪(招待講演)
  • Year and Date: 2010-09-22
• [Presentation] 炎症発癌におけるゲノム不安定性誘導機序の解析とその標的治療 (2009)
  • Author(s): 丸澤宏之、千葉勉
  • Organizer: 第37回日本臨床免疫学会総会東京ステーションコンファレンスシンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2009-11-14
• [Presentation] 消化器癌の発生過程において炎症が遺伝子異常の生成に果たす役割 (2009)
  • Author(s): 丸澤宏之
  • Organizer: 第51回日本消化器病学会大会・第13回日本肝臓学会大会JDDW2009国立京都国際会館シンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2009-10-15
• [Presentation] 肝幹/前駆細胞への遺伝子異常蓄積からの肝発癌機序. (2009)
  • Author(s): 高井淳、丸澤宏之、千葉勉
  • Organizer: 第51回日本消化器病学会大会・第13回日本肝臓学会大会JDDW2009国立京都国際会館ワークショップ
  • Place of Presentation: 京都
  • Year and Date: 2009-10-15
• [Presentation] 消化器癌の発生過程において炎症が遺伝子異常の生成に果たす役割 (2009)
  • Author(s): 丸澤宏之
  • Organizer: 第51回日本消化器病学会大会
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2009-10-15
• [Presentation] 慢性肝疾患からの肝癌発生の分子機序 (2008)
  • Author(s): 丸澤宏之
  • Organizer: 第12回日本肝臓学会大会
  • Place of Presentation: 東京
  • Year and Date: 2008-10-01