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Molecular analysis of mutated isocitrate dehydrogenase and its clinical application

Research Project

Project/Area Number 25462242
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurosurgery
Research InstitutionTohoku University

Principal Investigator

Kato Yukinari  東北大学, 医学(系)研究科(研究院), 教授 (00571811)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
KeywordsIDH / IDH1-R132H / glioma / モノクローナル抗体 / HMba-2 / HMab-2 / イソクエン酸デヒドロゲナーゼ / IDH1/2 / multi-specific mAb / MsMab-1 / 診断マーカー / 免疫組織染色
Outline of Final Research Achievements

Isocitrate dehydrogenase 1/2 (IDH1/2) mutations have been reported in gliomas, and are remarkably specific to a single codon in the conserved and functionally important arginine 132 residue (R132) of IDH1 or arginine 172 residue (R172) of IDH2. To date, we have established several monoclonal antibodies (mAbs) specific for IDH1/2 mutations. Here, we established MsMab-1 mAb that reacts with IDH1-R132H, IDH1-R132S, IDH1-R132G, and IDH2-R172M, but not with wild type IDH1/2. MsMab-1 stained the IDH1-R132S or IDH1-R132G -expressing glioma cells in immunohistochemistry. MsMab-1 is expected to be useful for immunohistochemical determination of IDH1/2 mutation-bearing tumors.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (21 results)

All 2015 2013 2012 Other

All Journal Article (13 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 13 results,  Acknowledgement Compliant: 5 results) Presentation (6 results) (of which Invited: 1 results) Remarks (2 results)

  • [Journal Article] A high-sensitive HMab-2 specifically detects IDH1-R132H, the most common IDH mutation in gliomas2015

    • Author(s)
      Fujii Y, Ogasawara S, Oki H, Liu X, Kaneko MK, Takano S, Kato Y
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 466 Issue: 4 Pages: 733-739

    • DOI

      10.1016/j.bbrc.2015.09.070

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Specific monoclonal antibodies against IDH1/2 mutations as diagnostic tools for gliomas.2015

    • Author(s)
      Kato Y
    • Journal Title

      Brain Tumor Pathol.

      Volume: 32 Issue: 1 Pages: 3-11

    • DOI

      10.1007/s10014-014-0202-4

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] A novel monoclonal antibody SMab-2 recognizes endogenous IDH2-R172S of chondrosarcoma2015

    • Author(s)
      Liu X, Ogasawara S, Kaneko MK, Oki H, Hozumi Y, Goto K, Takagi M, Kato Y.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 459 Issue: 4 Pages: 636-642

    • DOI

      10.1016/j.bbrc.2015.02.162

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Evaluation of IDH1 status in diffusely infiltrating gliomas by immunohistochemistry using anti-mutant and wild type IDH1 antibodies2015

    • Author(s)
      Ikota H, Nobusawa S, Arai H, Kato Y, Ishizawa K, Hirose T, Yokoo H.
    • Journal Title

      Brain Tumor Pathol.

      Volume: 32 Issue: 4 Pages: 237-244

    • DOI

      10.1007/s10014-015-0222-8

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Diagnostic advantage of double immunohistochemistry using two mutation-specific anti-IDH antibodies (HMab-1 and MsMab-1) in gliomas.2015

    • Author(s)
      Takano S, Kato Y, Yamamoto T, Liu X, Ishikawa E, Kaneko MK, Ogasawara S, Matsuda M, Noguchi M, Matsumura A.
    • Journal Title

      Brain Tumor Pathol.

      Volume: 32 Issue: 3 Pages: 169-175

    • DOI

      10.1007/s10014-015-0214-8

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Establishment of a Multi-Specific Monoclonal Antibody MsMab-1 Recognizing Both IDH1 and IDH2 Mutations2013

    • Author(s)
      Kaneko MK, Ogasawara S, Kato Y.
    • Journal Title

      The Tohoku Journal of Experimental Medicine

      Volume: 230 Issue: 2 Pages: 103-109

    • DOI

      10.1620/tjem.230.103

    • NAID

      10031182999

    • ISSN
      0040-8727, 1349-3329
    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Isocitrate dehydrogenase 2 mutation is a frequent event in osteosarcoma detected by a multi-specific monoclonal antibody MsMab-12013

    • Author(s)
      Liu X, Kato Y, Kaneko MK, Sugawara M, Ogasawara S, Tsujimoto Y, Naganuma Y, Yamakawa M, Tsuchiya T, Takagi M
    • Journal Title

      Cancer Med

      Volume: 2 Issue: 6 Pages: 803-814

    • DOI

      10.1002/cam4.149

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Multi-specific monoclonal antibody MsMab-2 recognizes IDH1-R132L and IDH2-R172M mutations.2013

    • Author(s)
      Ogasawara S, Kaneko MK, Tsujimoto Y, Liu X, Kato Y.
    • Journal Title

      Monoclon Antib Immunodiagn Immunother.

      Volume: 32 Issue: 6 Pages: 377-381

    • DOI

      10.1089/mab.2013.0050

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Novel monoclonal antibodies GMab-r1 and LMab-1 specifically recognize IDH1-R132G and IDH1-R132L mutations.2013

    • Author(s)
      Kaneko MK, Tsujimoto Y, Hozumi Y, Goto K, Kato Y.
    • Journal Title

      Monoclon Antib Immunodiagn Immunother.

      Volume: 32(3) Issue: 3 Pages: 224-228

    • DOI

      10.1089/mab.2013.0006

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Generation of a novel monoclonalantibody WMab-1 specific forIDH2-R172W mutation2013

    • Author(s)
      Kato Y, KanekoMK
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 19;433(4) Issue: 4 Pages: 374-8

    • DOI

      10.1016/j.bbrc.2013.02.106

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] A novel monoclonal antibody GMab-m1 specifically recognizes IDH1-R132G mutation.2013

    • Author(s)
      Kato Y, Natsume A, Kaneko MK.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 432 Issue: 4 Pages: 564-567

    • DOI

      10.1016/j.bbrc.2013.02.049

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Establishment of novel monoclonalantibodies KMab-1 and MMab-1 specificfor IDH2 mutations2013

    • Author(s)
      Kaneko MK, MoritaS, Tsujimoto Y, Yanagiya R, Nasu K,Sasaki H, Hozumi Y, Goto K, Natsume A,Watanabe M, Kumabe T, Takano S, KatoY
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 1;432(1) Issue: 1 Pages: 40-5

    • DOI

      10.1016/j.bbrc.2013.01.088

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Progressive adult primary glioblastoma in the medulla oblongata with an unmethylated MGMT promoter and without an IDH mutation2012

    • Author(s)
      Yoshikawa A, Nakada M, Watanabe T, Hayashi Y, Sabit H, Kato Y, Suzuki S, Ooi A, Sato H, Hamada JI
    • Journal Title

      Brain Tumor Pathol

      Volume: (in press) Issue: 3 Pages: 28-28

    • DOI

      10.1007/s10014-012-0118-9

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 変異型IDHに対する特異的抗体の開発2015

    • Author(s)
      加藤幸成
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(名古屋市)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 新規IDH2抗体による軟骨肉腫におけるIDH2-R172S変異の解析2015

    • Author(s)
      劉 興、小笠原諭、金子美華、大木弘治、加藤幸成
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(名古屋市)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] 変異型IDH1/2に対する新規抗体MsMab-1の樹立2013

    • Author(s)
      加藤幸成、小笠原諭、金子美華
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシィフィコ横浜(横浜市)
    • Related Report
      2013 Research-status Report
  • [Presentation] 変異型IDH1/2に対するMulti-specific抗体の作製2013

    • Author(s)
      加藤幸成、金子美華
    • Organizer
      第一回がんと代謝研究会
    • Place of Presentation
      鶴岡メタボロームキャンパス レクチャーホール(鶴岡市)
    • Related Report
      2013 Research-status Report
  • [Presentation] 骨肉腫における変異型イソクエン酸デヒドロゲナーゼの発現解析

    • Author(s)
      劉興、菅原正登、金子美華、小笠原諭、辻本雄太、長沼靖、土屋登嗣、高木理彰、加藤幸成
    • Organizer
      第33回日本分子腫瘍マーカー研究会
    • Place of Presentation
      パシィフィコ横浜(横浜市)
    • Related Report
      2013 Research-status Report
  • [Presentation] 変異型イソクエン酸デヒドロゲナーゼ1/2に対するMuti-specific抗体の作製

    • Author(s)
      辻本雄太、金子美華、小笠原諭、加藤幸成
    • Organizer
      第33回日本分子腫瘍マーカー研究会
    • Place of Presentation
      パシィフィコ横浜(横浜市)
    • Related Report
      2013 Research-status Report
  • [Remarks] 東北大学大学院医学系研究科地域イノベーション分野

    • URL

      http://www.med-tohoku-antibody.com/index.htm

    • Related Report
      2015 Annual Research Report
  • [Remarks] 東北大学大学院医学系研究科・加藤研究室

    • URL

      http://www.med-tohoku-antibody.com/

    • Related Report
      2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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