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Detection of purine metabolizing enzyme and its clinical use

Research Project

Project/Area Number 13557226
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Laboratory medicine
Research InstitutionMie University

Principal Investigator

SHIRAISHI Taizo  Mie University, Faculty of Medicine, Professor, 医学部, 教授 (30162762)

Co-Investigator(Kenkyū-buntansha) NOBORI Tsutomu  Mie University, Faculty of Medicine, Professor, 医学部, 教授 (60106995)
KOMADA Yoshihiro  Mie University, Faculty of Medicine, Professor, 医学部, 教授 (80186791)
TAKAO Motoshi  Mie University, Faculty of Medicine, Reseach Associate, 医学部, 助手 (30263007)
YAMAMORI Syunji  Mitsubishikagaku BCL, Gene Analysis, Director, 遺伝子解析部, 部長(研究職)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥12,900,000 (Direct Cost: ¥12,900,000)
Fiscal Year 2003: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2001: ¥5,600,000 (Direct Cost: ¥5,600,000)
KeywordsMTAP gene deficiency / Lung Cancer / Leukemia / Chemotherapy / PCR / Immunohistochemistry / MTAP / promoterのメチル化 / 非小細胞肺癌 / 定量的PCR法 / モノクロナール抗体 / 抗癌剤感受性試験 / Methylthioadenosine
Research Abstract

Materials were obtained with permission from patients who underwent operations for lung cancer. MTAP genetic analysis was carried out on 78 samples. IHC was carried out on 72 samples. MTAP gene was analyzed by real-time PCR while MTAP protein was detected by IHC. Methylation specific primers were used to analyze the promoter methylation MTAP gene on DNA treated with sodium bisulfate. 24 (32.9%) out of 73 samples were found to lack the MTAP gene. IHC was performed on 72 samples, since 6 samples were too small for evalucation with IHC. Out of 72 samples, 32 (44.4%) were found to be MTAP deficient with IHC. Of 47 samples tested positive with real-time PCR, 40 were MTAP positive but seven were negative with IHC. Twenty-three samples were MTAP negative with both real-time PCR and IHC. All 7 samples tested positive with real-time PCR, but negative with IHC were found to have the hypermethylated MTAP promoter, consisting of 23.3% in MTAP deficiency diagnosed with IHC. The reliability of the IHC-based diagnosis for MTAP deficiency was confirmed. This IHC method is applicable to formalin-fixed specimens. IHC was found to be specific enough to choose candidates for the selective chemotherapy targeting MTAP deficiency.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (10 results)

All 2003 2002 Other

All Journal Article (6 results) Publications (4 results)

  • [Journal Article] Molecular characterization of 5'-deoxy-5'-methylthioadenosine phosphorylase-deficient mutant clones of murine lymphoma cell line R1.12003

    • Author(s)
      Kadariya Yら
    • Journal Title

      Cancer Sci 43

      Pages: 519-522

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Molecular characterization of 5'-deoxy-5'-methylthioadenosine phosphorylase-deficient mutant clones of murinelymphoma cell line R1.1.2003

    • Author(s)
      Kadariya Y., et al.
    • Journal Title

      Cancer Sci. 43(6)

      Pages: 519-522

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Chemotherapy targeting methyl-thioadenosine phosphorylase (MTAP) deficiency in adult T cell leukemia(ATL).2002

    • Author(s)
      Harasawa Hら
    • Journal Title

      Leukemia 16

      Pages: 1799-1807

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Deletion of Dinucleotide repeat (Delta 14 allele) in the Methylthioadenosine phosphorylase (MTAP) promoterin the Japanese population2002

    • Author(s)
      Yuwaraj Kら
    • Journal Title

      Japanese Journal of Cancer Research 93

      Pages: 369-373

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Chemotherapy targeting methyl-thioadenosine phosphorylase (MTAP) deficiency in adult T cell leukemia(ATL).2002

    • Author(s)
      Harasawa H., Yamada Y., Kudoh M., Sugahara K., Soda H., Hirakata H., Ikeda S., Matsuo T., Tomonaga M., Nobori T., Kamihira S.
    • Journal Title

      Leukemia 16

      Pages: 1799-1807

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Deletion of Dinucleotide repeat (Delta 14 allele) in the Methylthioadenosine phosphorylase (MTAP) promoterin the Japanese population. (Japanese)2002

    • Author(s)
      Yuwaraj K., et al.
    • Journal Title

      Journal of Cancer Research

      Pages: 93369-93373

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kadariya Y., et al.: "Molecular characterization of 5'-deoxy-5'methylthioadenosine phosphorylase-deficient mutant clones of murine lymphoma cell line R1.1"Cancer Sci. 43・6. 519-522 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kadariya Y, et al.: "Deletion of Dinucleotide Repeat ( Δ 14 Allele) in the Methylthioadenosine Phosphorylase (MTAP) Promoter and Allelotype of MTAP Promoter in the Japanese Population"Japanese Journal of Cancer Research. 93・4. 369-373 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Harasawa H, et al.: "Chemotherapy targeting methylthioadenosine phosphorylase (MTAP) deficiency in adult T cell leukemia (ATL)"Leukemia. 16・10. 1799-1800 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yuwaraj K, et al.: "Deletion of Dinucleotide repeat (Delta 14 allele) in the Methylthio-adenosine phosphorylase (MTAP) promoterin the Japanese population"Japanese Journal of Cancer Research. (in press).

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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