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2012 Fiscal Year Final Research Report

Development of diagnostic tools for personalized cancer medicine by genomic and epigenomic analyses

Research Project

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Project/Area Number 22240090
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Tumor diagnosis
Research InstitutionTokyo Medical and Dental University

Principal Investigator

INAZAWA Johji  東京医科歯科大学, 難治疾患研究所, 教授 (30193551)

Co-Investigator(Kenkyū-buntansha) KOZAKI Kenichi  東京医科歯科大学, 難治疾患研究所, 准教授 (50270715)
INOUE Jun  東京医科歯科大学, 難治疾患研究所, 助教 (50568326)
Project Period (FY) 2010 – 2012
Keywords難治がん / 癌遺伝子 / 癌抑制遺伝子 / ゲノム / エピゲノム / マイクロRNA / DNAメチル化 / 分子標的薬
Research Abstract

In order to develop useful diagnostic tools for personalized cancer medicine, we performed genetic and epigenomic analyses in cancer, and identified novel cancer-related genes. By using methylation-based screening of tumor suppressor (TS) -miRNAs in oral squamous cell carcinoma (OSCC), we identified miR-596 and it target gene, LGALS3BP. Epithelial-mesenchymal transition (EMT) is relevant to the mechanism of invasion and metastasis in cancer. From a comprehensive gene expression analysis using colorectal cancer (CRC) cell lines, and following the ontology (GO) analysis, SIX1 was identified as an EMT-related gene in CRC. Furthermore, through DNA methylation and gene expression analyses of components in the Wnt signaling pathway, we identified WNT7A and WNT10A as genes silenced by mesenchymal-specific DNA hypermethylation in oral OSCC. In autophagy LC3 has a physiologically important role. Among LC3 family genes, we identified two transcriptional variants of LC3A, LC3Av1 and LC3Av2. Interestingly, we found that LC3Av1 functions in autophagy and indicated that LC3Av1 may be crucial in various types of cancer.

Research Products

(46 results)

All 2013 2012 2011 2010 Other

All Journal Article Presentation Book Remarks Patent(Industrial Property Rights)

  • [Journal Article] miR-655 is anEMT-suppressive microRNA targeting ZEB1 and TGFBR22013

    • Author(s)
      Harazono Y, Kozaki K, Muramatsu T, Endo H, Uzawa N, Kawano T, Harada K, Inazawa J
    • Journal Title

      PLoS One

      Volume: (in press)

    • Peer Reviewed
  • [Journal Article] The tumor-suppressive miR-497-195 cluster targets multiple cell-cycle regulators in hepatocellular carcinoma2013

    • Author(s)
      Furuta M, Kozaki K, Tanimoto K, TanakaS, Arii S, Shimamura T, Niida A, Miyano S, Inazawa J
    • Journal Title

      PLoS One

      Volume: 8 Pages: e60155

    • Peer Reviewed
  • [Journal Article] Potential oftumor-suppressive miR-596 targeting LGALS3BP as a therapeutic agent in oral cancer2013

    • Author(s)
      3. Endo H, Muramatsu T, Furuta M, UzawaN, Pimkhaokham A, Amagasa T, InazawaJ, Kozaki K
    • Journal Title

      Carcinogenesis

      Volume: 34 Pages: 560-9

    • DOI

      doi:10.1093/carcin/bgs376

    • Peer Reviewed
  • [Journal Article] Genomic copy-number alterations of MYC and FHIT genes are associated with survival in esophageal squamous-cell carcinoma2012

    • Author(s)
      Miyawaki Y, Kawachi H, Ooi A, Eishi Y, Kawano T, Inazawa J, Imoto I
    • Journal Title

      Cancer Sci

      Volume: 103 Pages: 1558-66

    • DOI

      doi:10.1016/j.humpath.2012.03.015

    • Peer Reviewed
  • [Journal Article] Integrative array-based approach identifies MZB1 as a frequently methylated putative tumor-suppressor in hepatocellular carcinoma2012

    • Author(s)
      Matsumura S, Imoto I, Kozaki K, Matsui T, Muramatsu T, Furuta M, Tanaka S, Sakamoto M, Arii S, Inazawa J
    • Journal Title

      Clin Cancer Res

      Volume: 18 Pages: 3541-3551

    • DOI

      doi:10.1158/1078-0432.CCR-11-1007

    • Peer Reviewed
  • [Journal Article] Common variants at 11q12, 10q26 and 3p11.2 are associated with prostate cancer susceptibility in Japanese2012

    • Author(s)
      Akamatsu S, Takata R, Haiman CA, Takahashi A, Inoue T, Kubo M, Furihata M, Kamatani N, Inazawa J, Chen GK, Le Marchand L, Kolonel LN, Katoh T,Yamano Y, Yamakado M, Takahashi H, Yamada H, Egawa S, Fujioka T, Henderson BE, Habuchi T, Ogawa O, Nakamura Y, Nakagawa H
    • Journal Title

      Nat Genet

      Volume: 44 Pages: 426-9

    • DOI

      doi:10.1038/ng.1104

    • Peer Reviewed
  • [Journal Article] SIX1 promotes epithelial-mesenchymal transition in colorectal cancer through ZEB1activation2012

    • Author(s)
      Ono H, Imoto I, Kozaki K, Tsuda H, Matsui T, Kurasawa Y, Muramatsu T, Sugihara K, Inazawa J
    • Journal Title

      Oncogene

      Volume: 31 Pages: 4923-34

    • DOI

      doi:10.1038/onc.2011.646

    • Peer Reviewed
  • [Journal Article] A transcriptional variant of the LC3A gene is involved in autophagy andfrequently inactivated in human cancers2012

    • Author(s)
      Bai H, Inoue J, Kawano T, Inazawa J
    • Journal Title

      Oncogene

      Volume: 31 Pages: 4397-408

    • DOI

      doi:10.1038/onc.2011.613

    • Peer Reviewed
  • [Journal Article] Stabilization of phenotypic plasticity through mesenchymal- specific DNA hypermethylation in cancer cells2012

    • Author(s)
      Kurasawa Y, Kozaki K, Pimkhaokham A, Muramatsu T, Ono H, Ishihara T, Uzawa N, Imoto I, Amagasa T, Inazawa J
    • Journal Title

      Oncogene

      Volume: 31 Pages: 1963-74

    • DOI

      doi:10.1038/onc.2011.373

    • Peer Reviewed
  • [Journal Article] HECT-type ubiquitin ligase ITCH targets lysosomal- associated protein multispanningtransmembrane 5 (LAPTM5) and prevents LAPTM5-mediated cell death2011

    • Author(s)
      Ishihara T, Inoue J, Kozaki K, Imoto I, Inazawa J
    • Journal Title

      J Biol Chem

      Volume: 286 Pages: 44086-94

    • DOI

      doi:10.1074/jbc.M111.251694

    • Peer Reviewed
  • [Journal Article] miR-152 is a tumor suppressor microRNA that is silenced by DNA hypermethylation in endometrial cancer2011

    • Author(s)
      Tsuruta T, Kozaki K, Uesugi A, Furuta M, Hirasawa A, Imoto I, Susumu N, Aoki D, Inazawa J
    • Journal Title

      Cancer Res

      Volume: 71 Pages: 6450-62

    • DOI

      doi:10.1158/0008-5472.CAN-11-0364

    • Peer Reviewed
  • [Journal Article] The tumor suppressive microRNA miR-218 targets the mTOR component Rictor and inhibits AKT phosphorylation in oral cancer2011

    • Author(s)
      Uesugi A, Kozaki K, Tsuruta T, FurutaM, Morita K, Imoto I, Omura K, InazawaJ
    • Journal Title

      Cancer Res

      Volume: 71 Pages: 5765-78

    • DOI

      doi:10.1158/0008-5472.CAN-11-0368

    • Peer Reviewed
  • [Journal Article] YAP is a candidate oncogene for esophageal squamous-cell carcinoma2011

    • Author(s)
      Muramatsu T, Imoto I, Matsui T, Kozaki K, Haruki S, Sudol M, Shimada Y, Tsuda H, Kawano T, Inazawa J
    • Journal Title

      Carcinogenesis

      Volume: 32 Pages: 389-98

    • DOI

      doi:10.1093/carcin/bgq254

    • Peer Reviewed
  • [Journal Article] Variation in TP63 is associated with lung adenocarcinoma susceptibility inJapanese and Korean populations2010

    • Author(s)
      Miki D, Kubo M, Takahashi A, Yoon KA, Kim J, Lee GK, Zo JI, Lee JS, Hosono N, Morizono T, Tsunoda T, Kamatani N, Chayama K, Takahashi T, Inazawa J, Nakamura Y, Daigo Y
    • Journal Title

      NatGenet

      Volume: 42 Pages: 893-6

    • DOI

      doi:10.1038/ng.667

    • Peer Reviewed
  • [Journal Article] Genome-wide association study identifies five new susceptibility loci for prostate cancer in the Japanese population2010

    • Author(s)
      Takata R, Akamatsu S, Kubo M, Takahashi A, Hosono N, Kawaguchi T, Tsunoda T, Inazawa J, Kamatani N,Ogawa O, Fujioka T, Nakamura Y, Nakagawa H
    • Journal Title

      Nat Genet

      Volume: 42 Pages: 751-4

    • DOI

      doi:10.1038/ng.635

    • Peer Reviewed
  • [Journal Article] Frequent silencing of protocadherin 17, a candidate tumour suppressor for esophageal squamous-cell carcinoma2010

    • Author(s)
      Haruki S, Imoto I, Kozaki K, Matsui T, Kawachi H, Komatsu S, Muramatsu T, Shimada Y, Kawano T, Inazawa J
    • Journal Title

      Carcinogenesis

      Volume: 31 Pages: 1027-36

    • DOI

      doi:10.1093/carcin/bgq053

    • Peer Reviewed
  • [Journal Article] miR-124 andmiR-203 are epigenetically silenced tumor-suppressive microRNAs in hepatocellular carcinoma2010

    • Author(s)
      Furuta M, Kozaki K, Tanaka S, Arii S, Imoto I, Inazawa J
    • Journal Title

      Carcinogenesis

      Volume: 31 Pages: 766-76

    • DOI

      doi:10.1093/carcin/bgp250

    • Peer Reviewed
  • [Presentation] Exploring of tumor suppressive micro-RNAs silenced by tumor-specific DNA hypermethylation in cancer2013

    • Author(s)
      Inazawa J
    • Organizer
      The 22^<nd> HCS/the 4^<th> JARI Joint International Symposium
    • Place of Presentation
      Hiroshima, Japan
    • Year and Date
      2013-08-30
  • [Presentation] Identification oftumor-suppressor micro-RNAs silenced by DNA hypermethylation in cancer2012

    • Author(s)
      Inazawa J
    • Organizer
      2012 Seoul National University Cancer Research Institute Symposium
    • Place of Presentation
      Seoul National University Kwanak Campus, Culture Center, Seoul, South Korea
    • Year and Date
      20120516-19
  • [Presentation] 新世代ゲノム解析技術によって浮上するがんのバックシートドライ バー2012

    • Author(s)
      稲澤讓治
    • Organizer
      第16回日本がん分子標的治療学会
    • Place of Presentation
      西日本総合展示場.福岡
    • Year and Date
      2012-06-29
  • [Presentation] Exploring of tumor suppressor micro RNAs silenced by DNA methylation2011

    • Author(s)
      Inazawa J
    • Organizer
      9^<th> China-Japan Joint Conference of Cancer
    • Place of Presentation
      Shanghai, China
    • Year and Date
      20111121-23
  • [Presentation] がんの統合的ゲノム・エピゲノム解析の最近の進歩2011

    • Author(s)
      稲澤讓治
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場.愛知
    • Year and Date
      2011-10-05
  • [Presentation] Integrative genomics andepigenomics for identification of cancer-related genes2010

    • Author(s)
      Inazawa J
    • Organizer
      Linking systems-biology to cancer research. Seoul national university dental hospital. Seoul
    • Place of Presentation
      Korea
    • Year and Date
      2010-11-06
  • [Presentation] LAPTM5蓄積で誘導されるリ ソゾーム細胞死と神経芽腫の自然退縮機構2010

    • Author(s)
      稲澤譲治
    • Organizer
      がん特定研究5領域合同シンポジウム
    • Place of Presentation
      学術総合センター・一橋記念講堂.東京
    • Year and Date
      2010-01-14
  • [Book] 株式会社南江堂(東京)2012

    • Author(s)
      稲澤譲治
    • Total Pages
      8-13
    • Publisher
      新臨床腫瘍学(改訂第3版)-がん薬物療法専門医のために-
  • [Book] 独立行政法人科学技術振興機構中国総合研究センター(東京)2011

    • Author(s)
      稲澤讓治
    • Total Pages
      603
    • Publisher
      中国・日本科学最前線-研究の現場から- 2011年版
  • [Book] 株式会社羊土社(東京)2011

    • Author(s)
      稲澤讓治
    • Total Pages
      140-150
    • Publisher
      がん生物学イラストレイテッド
  • [Book] 日本医師会雑誌2010

    • Author(s)
      稲澤譲治
    • Total Pages
      562-566
    • Publisher
      染色体異常-検査の進歩、結果の解釈.日本医師会
  • [Remarks] 東京医科歯科大学難治疾患研究所分子細胞遺伝ホームページ

    • URL

      http://www.tmd.ac.jp/mri/cgen/framepage.htm

  • [Patent(Industrial Property Rights)] 卵巣癌の検出方法、及び抑制方法2012

    • Inventor(s)
      稲澤譲治、井本逸勢、菊池良子
    • Industrial Property Rights Holder
      国立大学法人東京医科歯科大学、富 士フイルム株式会社
    • Industrial Property Number
      13/659.834
    • Filing Date
      2012-10-24
    • Overseas
  • [Patent(Industrial Property Rights)] 食道癌の検出方法2012

    • Inventor(s)
      稲澤譲治、小崎健一、井本逸勢
    • Industrial Property Rights Holder
      国立大学法人東京医科歯科大学、株式会社ビー・エム・エル
    • Industrial Property Number
      特許第5044837号
    • Acquisition Date
      2012-07-27
  • [Patent(Industrial Property Rights)] 癌抑制剤2012

    • Inventor(s)
      稲澤譲治、井本逸勢、和泉宏幸、横井左奈
    • Industrial Property Rights Holder
      国立大学法人東京医科歯科大学、富士フイルム株式会社
    • Industrial Property Number
      特許第5002749号
    • Acquisition Date
      2012-06-01
  • [Patent(Industrial Property Rights)] 卵巣癌の検出方法、及び抑制方法2012

    • Inventor(s)
      稲澤譲治、井本逸勢、菊池良子
    • Industrial Property Rights Holder
      国立大学法人東京医科歯科大学、富 士フイルム株式会社
    • Industrial Property Number
      1997910
    • Acquisition Date
      2012-08-15
    • Overseas
  • [Patent(Industrial Property Rights)] 神経芽腫の検出方法2012

    • Inventor(s)
      稲澤譲治、井本逸勢、井上純
    • Industrial Property Rights Holder
      国立大学法人東京医科歯科大学、富 士フイルム株式会社
    • Industrial Property Number
      8216785
    • Acquisition Date
      2012-07-10
    • Overseas
  • [Patent(Industrial Property Rights)] 癌の検出方法および癌抑制剤2012

    • Inventor(s)
      稲澤譲治、小崎健一、井本逸勢
    • Industrial Property Rights Holder
      国立大学法人東京医科歯科大学、富 士フイルム株式会社
    • Industrial Property Number
      8183223
    • Acquisition Date
      2012-05-22
    • Overseas
  • [Patent(Industrial Property Rights)] 口腔扁平上皮癌の検出方法2012

    • Inventor(s)
      稲澤譲治、井本逸勢、中村恵理奈、 津田均
    • Industrial Property Rights Holder
      国立大学法人東京医科歯科大学、富 士フイルム株式会社
    • Industrial Property Number
      8143003
    • Acquisition Date
      2012-03-27
    • Overseas
  • [Patent(Industrial Property Rights)] 癌抑制剤2012

    • Inventor(s)
      稲澤譲治、井本逸勢、和泉宏幸、横井左奈
    • Industrial Property Rights Holder
      国立大学法人東京医科歯科大学、富 士フイルム株式会社
    • Industrial Property Number
      1837399
    • Acquisition Date
      2012-06-22
    • Overseas
  • [Patent(Industrial Property Rights)] 癌の検出方法および癌抑制剤2012

    • Inventor(s)
      稲澤譲治、小崎健一、井本逸勢
    • Industrial Property Rights Holder
      国立大学法人東京医科歯科大学、富 士フイルム株式会社
    • Industrial Property Number
      2088208
    • Acquisition Date
      2012-04-27
    • Overseas
  • [Patent(Industrial Property Rights)] 癌の検出方法および抑制方法2012

    • Inventor(s)
      稲澤譲治、井本逸勢、于衛
    • Industrial Property Rights Holder
      国立大学法人東京医科歯科大学、富 士フイルム株式会社
    • Industrial Property Number
      7867709
    • Acquisition Date
      2012-01-11
    • Overseas
  • [Patent(Industrial Property Rights)] 癌抑制剤2011

    • Inventor(s)
      稲澤譲治、井本逸勢、于衛
    • Industrial Property Rights Holder
      国立大学法人東京医科歯科大学、富士フイルム株式会社
    • Industrial Property Number
      特許第4867018号
    • Acquisition Date
      2011-11-25
  • [Patent(Industrial Property Rights)] 癌の検出方法および抑制方法2010

    • Inventor(s)
      稲澤譲治、小崎健一、井本逸勢
    • Industrial Property Rights Holder
      国立大学法人東京医科歯科大学、富士フイルム株式会社
    • Industrial Property Number
      12/964.464
    • Filing Date
      2010-12-09
    • Overseas
  • [Patent(Industrial Property Rights)] 核酸マイクロアレイの異常スポットを 検出する方法2010

    • Inventor(s)
      稲澤譲治、井本逸勢
    • Industrial Property Rights Holder
      国立大学法人東京医科歯科大学、富 士フイルム株式会社
    • Industrial Property Number
      2010-118362
    • Filing Date
      2010-05-24
  • [Patent(Industrial Property Rights)] 核酸マイクロアレイの異常スポットを 検出する方法2010

    • Inventor(s)
      稲澤譲治、井本逸勢
    • Industrial Property Rights Holder
      国立大学法人東京医科歯科大学、富 士フイルム株式会社
    • Industrial Property Number
      12/787.953
    • Filing Date
      2010-05-26
    • Overseas
  • [Patent(Industrial Property Rights)] 核酸マイクロアレイの異常スポットを検出する方法2010

    • Inventor(s)
      稲澤譲治、井本逸勢
    • Industrial Property Rights Holder
      国立大学法人東京医科歯科大学、富士フイルム株式会社
    • Industrial Property Number
      10164051.4
    • Filing Date
      2010-05-27
    • Overseas
  • [Patent(Industrial Property Rights)] 核酸マイクロアレイの異常スポットを 検出する方法2010

    • Inventor(s)
      稲澤譲治、井本逸勢
    • Industrial Property Rights Holder
      国立大学法人東京医科歯科大学、富士フイルム株式会社
    • Industrial Property Number
      10164051.4
    • Filing Date
      2010-05-27
    • Overseas
  • [Patent(Industrial Property Rights)] 癌抑制剤2010

    • Inventor(s)
      稲澤譲治、井本逸勢、和泉宏幸、横井左奈
    • Industrial Property Rights Holder
      国立大学法人東京医科歯科大学、富 士フイルム株式会社
    • Industrial Property Number
      7691594
    • Acquisition Date
      2010-04-06
    • Overseas

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Published: 2014-08-29  

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