Global anallysis of genetic and epigenetic alterations during inflammation-associated gastrointestinal cancer development, and elucidation of its mechanism
Project/Area Number |
24229005
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Research Category |
Grant-in-Aid for Scientific Research (S)
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Allocation Type | Single-year Grants |
Research Field |
Gastroenterology
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Research Institution | Kyoto University |
Principal Investigator |
CHIBA Tsutomu 京都大学, 医学(系)研究科(研究院), 教授 (30188487)
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Co-Investigator(Kenkyū-buntansha) |
MARUSAWA Hiroyuki 京都大学, 医学研究科, 講師 (80324630)
WATANABE Tomohiro 京都大学, 医学研究科, 准教授 (40444468)
USHIJIMA Toshikazu 独立行政法人国立がん研究センター, 研究所 (90232818)
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Project Period (FY) |
2012-05-31 – 2015-03-31
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Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥171,730,000 (Direct Cost: ¥132,100,000、Indirect Cost: ¥39,630,000)
Fiscal Year 2014: ¥53,040,000 (Direct Cost: ¥40,800,000、Indirect Cost: ¥12,240,000)
Fiscal Year 2013: ¥53,560,000 (Direct Cost: ¥41,200,000、Indirect Cost: ¥12,360,000)
Fiscal Year 2012: ¥65,130,000 (Direct Cost: ¥50,100,000、Indirect Cost: ¥15,030,000)
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Keywords | AID / 炎症発癌 / 癌幹細胞 / 組織幹細胞 / エピゲノム / 遺伝子変異 / ゲノム異常 / エピゲノム異常 / H.Pylori / HCV |
Outline of Final Research Achievements |
Infection and/or inflammation play important roles in the development of various cancers in digestive organs. We have previously demonstrated that activation-induced cytidine deaminase (AID), a DNA editing enzyme, is involved in inflammation-associated carcinogenesis through induction of various mutations. In the present study, by using ultra-deep sequencer we serially analyzed genetic and epigenetic changes during cancer development with the background of inflammation in both human and mice. As a result, we demonstrated that AID has crucial roles in the induction of not only genetic but also epigenetic changes during inflammation-induced carcinogenesis.
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Assessment Rating |
Verification Result (Rating)
A-
Result (Rating)
A-: Progress in the research is steadily towards the initial goal. However, further efforts are necessary as a part of the research progress is delayed.
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Report
(7 results)
Research Products
(51 results)
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[Journal Article] Leptin receptor somatic mutations are frequent in HCV-infected cirrhotic liver and associated with hepatocellular carcinoma.2014
Author(s)
Ikeda A, Shimizu T, Matsumoto Y, Fujii Y, Eso Y, Inuzuka T, Mizuguchi A, Shimizu K, Hatano E, Uemoto S, Chiba T, Marusawa H
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Journal Title
Gastroenterology
Volume: 146
Issue: 1
Pages: 222-232
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] A model of liver carcinogenesis originating from hepatic progenitor cells with accumulation of genetic alterations.2014
Author(s)
Soo Ki Kim, Akihiro Nasu, Junji Komori, Takahiro Shimizu, Yuko Matsumoto, Yasuko Minaki, Kenji Kohno, Kazuharu Shimizu, Shinji Uemoto, Tsutomu Chiba, Hiroyuki Marusawa.
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Journal Title
International Journal of Cancer
Volume: 134
Issue: 5
Pages: 1067-76
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] NOD2 downregulates colonic inflammation by IRF4-mediated inhibition of K63-linked polyubiquitination of RICK and TRAF6.2014
Author(s)
Watanabe T, Asano N, Meng G, Yamashita K, Arai Y, Sakurai T, Kudo M, Fuss IJ, Kitani A, Shimosegawa T, Chiba T, Strober W.
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Journal Title
Mucosal Immunol
Volume: 1
Issue: 6
Pages: 1-1
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Modelling mutational landscapes of human cancers in vitro.2014
Author(s)
Olivier M, Weninger A, Ardin M, Huskova H, Castells X, Vallee MP, McKay J, Nedelko T, Muehlbauer KR, Marusawa H, Alexander J, Hazelwood L, Byrnes G, Hollstein M, Zavadil J
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Journal Title
Sci Rep
Volume: 4
Issue: 1
Pages: 4482-4482
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Accumulation of somatic mutations in TP53 in gastric epithelium with Helicobacter pylori infection.2014
Author(s)
Shimizu T, Marusawa H, Matsumoto Y, Inuzuka T, Ikeda A, Fujii Y, Minamiguchi S, Miyamoto S, Kou T, Sakai Y, Crabtree JE, Chiba T.
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Journal Title
Gastroenterology
Volume: 147
Issue: 2
Pages: 407-417
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] REG Iα is a biomarker for predicting response to chemotherapy S-1 plus cisplatin in patients with unresectab le stage IV gastric cancer.2013
Author(s)
Sekikawa A, Fukui H, Zhang X, Maruo T, Tsumura T, Okabe Y, Wakasa T, Osaki Y, Chiba T, Tomita T, Oshima T, Watari J, Miwa H.
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Journal Title
Br J Cancer.
Volume: 108(2)
Issue: 2
Pages: 395-401
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] 炎症と遺伝性不安定性2013
Author(s)
千葉 勉、丸澤宏之
Organizer
第72回日本癌学会学術集会
Place of Presentation
パシフィコ横浜
Year and Date
2013-10-03
Related Report
Invited
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