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The identification of the genes involved in the development and progression of multiple osteo chondromas.

Research Project

Project/Area Number 02454344
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Orthopaedic surgery
Research InstitutionKyoto University

Principal Investigator

KOTOURA Yoshihiko  Department of Orthopaedic Surgery, Kyoto University Associate professor, 医学部, 助教授 (50127081)

Co-Investigator(Kenkyū-buntansha) ISHIZAKI Kanji  Radiation Biology Kyoto University Centoer, Kyoto University Associate Professor, 放射線生物研究センター, 助教授 (70111987)
SASAKI Masao  Radiation Biology Center. Professor, 放射線生物研究センター, 教授 (20013857)
Project Period (FY) 1990 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 1991: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1990: ¥3,900,000 (Direct Cost: ¥3,900,000)
Keywordsmultiple exostosis / linkage analysis / loss of heterozygosity / p53 tumor suppressor gene / p53癌抑制遺伝子 / 脱分化型軟骨肉腫 / linkage analysis / 染色体分析 / ヘテロ接合性消失
Research Abstract

Multiple exostosis is an autosomal dominant hereditary disease characterized by multiple osteochondromas affecting many bones. Although these tumors are benign in nature, approximately 10% of patients with multiple osteochondromas develop secondary Chondrosarcomas. In this research, two different approaches have been taken to analyze this disease. First, the linkage analysis using polymorphic DNA markers was performed to localize the gene causing this disease. 14 patients and 17 unaffected relatives from 8 different families with multiple exostosis have been analyzed using 7 polymorphic markers. This approach, however, has not yet been successful to identify the marker tightly linked to this disease, mainly due to the insufficient number of samples. The second approach is to identify chromosome arms where tumor cells lost the constitutional heterozygosity (LOH). which have been successf ully used to isolate the responsible genes for some hereditary tumors. 17 different chromosome arms were analyzed in 17 chondrosarcomas, and we found that 40% of tumors lost constitutional heterozygosity at the polymorphic markers on 17p. All cases with LOH on 17p were highly malignant tumors including 3 cases of dedifferentiated chondrosarcomas. The frequent LOH on 17p suggests the involvement of p53 tumor suppressor gene which is known to locate in this region. Subsequent analysis of the p53 gene in chondrosarcomas showed a point mutation in for cases with LOH on 17p, suggesting that the LOH on 17p in chondrosarcomas are related to the p53 gene mutation. Our results in this research suggest that because none of low grade chondrosarcomas showed alterations of the p53 gene, the mutations of the p53 gene may not be the initial genetic alteration in the development of chondrosarcoma, but rather involved in the progression of tumors. The mutation analysis of the p53 gene will be applicable for estimating the biological activities of chondrosarcomas.

Report

(3 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • Research Products

    (9 results)

All Other

All Publications (9 results)

  • [Publications] 山口 寿一: "Allelotype analysis in osteosarcoma;frequent allele loss on 3q,13q,17q,and 18q." Cancer Research. (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 戸口田 淳也: "Prevelance and spectrum of germーline p53 gene mutations among patients with sarcoma." New England Journal of Medeine. (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 戸口田 淳也: "Mutation spectrum of the p53 gene in bone and soft tissue sarcomas."

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Yamaguchi, T., et al.: "Allelotype analysis in osteosarcoma ; frequent allele loss on 3q, 13q, 17q, and 18q." Cancer Research.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Toguchida, J., et al.: "Prevelance and spectrum of germ-line p53 gene mutations among patients with sarcomas" New England Journal of Medicine.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Toguchida, J., et al.: "Mutation spectrum of the p53 gene in bone and soft tissue Sarcomas."

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 山口 寿一: "Allelotype analysis in osteosarcoma;frequent allele loss on 3q,13q,17q,and 18q." Cancer Research. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] 戸口田 淳也: "Prevelance and spectrum of germーline p53 gene mutations among patients with Sarcoma." New England Journal of Medecine. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] 戸口田 淳也: "Mutation spectrum of the p53 gene in bone and soft tissue sarcomas."

    • Related Report
      1991 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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