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Establishment of genetic diagnostics of brain tumors : Rapid diagnosis of mutation of p53 tumor suppressor gene.

Research Project

Project/Area Number 08457355
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

SAWAMURA Yutaka  Hosp., Hokkaido Univ., Lecturer, 医学部・附属病院, 講師 (10235476)

Co-Investigator(Kenkyū-buntansha) TADA Mitsuhiro  Sch.of Med., Hokkaido Univ., Assistant, 医学部, 助手 (10241316)
加藤 功  北海道大学, 医学部, 助手 (50271664)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1998: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1997: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1996: ¥6,000,000 (Direct Cost: ¥6,000,000)
Keywordsp53 / genetic diagnosis / yeast p53 functional assay / astrocytoma / glioblastoma / brain tumor / prognosis / gene diagnosis
Research Abstract

This project has yielded a considerable amount of results as follows.
1) Analysis of astrocytomas, where matching tumor material and derived cell lines were available, demonstrated a clonal expansion of p53 mutated clone, supporting the hypothesis of clonal progression of brain tumors in vivo (Int J Cancer 1996).
2) Application of the assay on anaplastic astrocytomas and glioblastomas demonstrated a higher ratio of p53 mutation in anaplastic astrocytomas (67%) than in glioblastomas (43%), indicating that that many glioblastomas develop by p53-independent pathways (Mol Carcinog 1997).
3) Analysis of clinicopathological parameters in patients with glioblastomas demonstrated that p53 mutation is a marker for better radiation response in glioblastomas and this results in significantly longer survival (Cancer Res 1998)
4) Application of the assay to non-astrocytic brain tumors demonstrated that p53 mutation is rare event except in primary malignant lymphomas (Acta Neuropathol 1998).
5) Analysis of pilocytic astrocytomas demonstrated that p53 mutation is rare in these tumors (Int J Cancer 1998).
6) By summarizing the above results, we have published several
review articles, including a chapter in a book.

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Tada M: "Clonality and stability of the p53 gene in human astrocytic tumor cells‐ Quantitative analysis of p53 gene mutations by yeast functional assay." International Journal of Cancer. 67. 447-450 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tada M: "Reappraisal of p53 Mutations in Human Malignant Astrocytic Neoplasms by p53 Functional Assay- Comparison with the Conventional Structural analyses." Molecular Carcinogenesis. 18. 171-176 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tada M: "Monitoring adenoviral p53 transduction efficiency by yeast functional assay." Gene Therapy. 5. 339-344 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nozaki M: "Rare occurrence of p53 gene mutation in non-astrocytic brain tumors-Reappraisal by yeast functional assay." Acta Neuropathologica. 95. 291-296 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tada M: "Selective sensitivity to rediation of cerebral glioblastomas harboring p53 mutation." Cancer Reserach. 58. 1793-1797 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nozaki M: "Expression study of oncogenic molecules in primary central nervous system lymphomas in immunocompetent patients." Acta Neuropathologica. 95. 505-510 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 多田光宏: "p53の変異とその機能的影響" 佐谷秀行監修 : p53-癌抑制の分子メカニズムと臨床応用, 秀潤社, 142 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tada M,et al.: "Clonality and stability of the p53 gene in human astrocytic tumor cells-Quantitative analysis of p53 gene mutations by yeast functional assay" Int J Cancer. 67. 447-450 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tada M,et al.: "Reappraisal of p53 Mutations in Human Malignant Astrocytic Neoplasms by p53 Functional Assay--Comparison with the Conventional Structural analyses." Mol Carcinog. 18. 171-176 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tada M,et al.: "Monitoring adenoviral p53 transduction efficiency by yeast functional assay." Gene Therapy. 5. 339-344 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nozaki M,et al.: "Rare occurrence of p53 gene mutation in non-astrocytic brain tumors-Reappraisal by yeast functional assay." Acta Neuropathol. 95. 291-296 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tada M,et al.: "Selective sensitivity to radiation of cerebral glioblastomas harboring p53 mutation." Cancer Res. 58. 1793-1797 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nozaki M,et al.: "Expression study of oncogenic molecules in primary central nervous system lymphomas in immunocompetent patients." Acta Neuropathol. 95. 505-510 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tada M: p53 mutation and its functional influences.Saya H (eds) "p53-Molecular Mechanisms and Clinical Applications, Shujunsha, Tokyo, 140 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nozaki M: "Rare occurrence of p53 gene mutation in non-astrocytic brain tumors-Reappraisal by yeast functional assay." Acta Neuropathologica. 95. 291-296 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Fujimoto H: "Significant correlation of nitric oxide synthase activity and p53 gene mutation in stage I lung adenocarcinoma." Japanese Journal of Cancer Research. 89. 696-702 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ishii N: "Absence of p53 gene mutations in a tumor panel representative of pilocytic astrocytoma diversity using a p53 functional assay." International Journal of Cancer. 76. 797-800 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tada M: "Selective sensitivity to radiation of cerebral glioblastomas harboring p53 mutation." Cancer Reserach. 58. 1793-1797 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tada M: "Monitoring adenoviral p53 transduction efficiency by yeast functional assay." Gene Therapy. 5. 339-344 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nozaki M: "Roles of the functional loss of p53 and other genes in astrocytoma tumorigenesis and progression." Neurooncology. 1(3)(in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 多田光宏: "p53の変異とその機能的影響" 佐谷秀行監修:p53-癌抑制の分子メカニズムと臨床応用,秀潤社, 142 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tada M: "Clonality and stability of the p53 gene in human astrocytic tumor cells." International Journal of Cancer. 67. 447-450 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tada M: "Homozygous p53 gene mutation in a radiation-induced glioblastoma." Neurosurgery. 40. 393-396 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tada M: "Reappraisal of p53 Mutations in Human Malignant Astrocytic Neoplasms." Molecular Carcinogenesis. 18. 171-176 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Murata J-I: "Nitric oxide as a carcinogen-analysis of inactivating p53 gene mutations…" Mutation Research. 41. 211-218 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nozaki M: "Rare occurrence of p53 gene mutation in non-astrocytic brain tumors." Acta Neuropathol.(印刷中). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ishii N: "Absence of p53 gene mutations in a tumor panel representative of pilocytic astrocytoma…" International Journal of Cancer.(印刷中). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tada M,: "Clonality and stability of the p53 gene in human astrocytic tumor cells." International Journal of Cancer. 67. 447-450 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tada M,: "Homozygous p53 gene mutation in a radiation-induced glioblastoma." Neurosurgery. 40. 393-396 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tada M,: "Reappraisal of p53 Mutations in Human Malignant Astrocytic Neoplasms." Molecular Carcinogenesis. (in press). (1997)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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