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Deletion Mapping of Chromosomes in Malignant Lymphoma and Molecular Cloning of a Putative Novel Tumor Suppressor Gene from the Loci

Research Project

Project/Area Number 09671104
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionNagoya University

Principal Investigator

KINOSHITA Tomohiro  School of Medicine, Nagoya University Assistant Professor, 医学部, 助手 (60283446)

Co-Investigator(Kenkyū-buntansha) NAGAI Hirokazu  School of Medicine, Medical Staff, 医学部, 医員
MURATE Takashi  School of Medicine, Assistant Professor, 医学部, 助教授 (30239537)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1998: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1997: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsMALIGNANT LYMPHOMA / TUMOR SUPPRESSOR GENE / LOH / WAF1 / B-CELL / YAC / 染色体
Research Abstract

Allelic deletions have been thought to be indicators of the presence of tumor suppressor genes (TSGs). As indicated by this allelotype study using 39 highly informative microsatellite markers distributed among all autosomal chromosomes, frequent loss of heterozygosity (LOH) has been found at 6p in B-cell non-Hodgkin lymphoma. To identify the common deleted regions (CDRs), we performed fine deletion mapping using 26 highly polymorphic microsatellite markers on 6p. The most frequent LOH occurred at D6S1721, where 9 of 18 of the informative cases (50%) had allelic losses. Seventeen of 32 cases (53%) exhibited LOH at least at one locus on 6p. Ten of these 17 cases showed interstitial deletions, and their LOH patterns indicated two CDRs on 6p ; one between D6S1721 and D6S260 (at 6p23-24), the other between D6S265 and D6S291 (at 6p21). The genetic distance of both CDRs was 6 cM.The CDKN1A (p21) is reported to be located within the interval of the CDR at 6p21, but no mutation of the gene was found in these 32 patients. These data suggested that these two loci might harbor novel putative TSGs responsible for the pathogenesis of malignant lymphoma. We have constructed a contig of yeast artificial chromosome (YAC) clones spanning the most frequent CDR at 6p23-24. This YAC contig can be used for fine physical mapping of the region and cloning of the candidate TSGs.

Report

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

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Nagai H.,Kinoshita T.,Suzuki H.,et al.: "Identification and Mapping of Novel Tumor Suppressor Loci on 6p in Diffuse Large B-cell non-Hodgkin Lymphoma" Genes,Chromosomes & Cancer. 発表予定.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tomita A.,Watanabe T.,Kinoshita T.,et al.: "Truncated c-Myb expression in the human leukemia cell line TK-6" Leukemia. 12. 1422-1429 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakahara Y.,Nagai H.,Kinoshita T.,et al.: "Mutational analysisi of the PTEN/MMAC1 gene in non-Hodgkin's lymphoma" Leukemia. 12. 1277-1280 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Uchida T.,Kinoshita T.,Nagai H.,et al.: "Hypermethylation of the p15^<INK4B> gene in myelodysplastic syndromes" Blood. 90. 1403-1409 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ichikawa A.,Kinoshita T.,Watanabe T.,et al.: "Mutations of the p53 gene as a prognostic factor in aggressive B-cell lymphoma." N.Engl.J.Med.337. 529-534 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kurokawa T.,Kinoshita T.,Murate T.,et al.: "Complementarity determining region-III is a useful molecular marker for the evaluation of minimal residual disease in mantle cell lymphoma." Br.J.Haematol.98. 408-412 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 木下朝博、永井宏和 他: "悪性リンパ腫の発症・進展と癌抑制遺伝子 血液・腫瘍科" 科学評論社, 160-166 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kurokawa T., KinoshitaT., Murate T., et al.: "Complementarity determining region-III is a useful molecular marker for the evaluation of minimal residual disease in mantle cell lymphoma." Br.J.Haematol.98. 408-412 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ichikawa A., Kinoshita T., Watanabe T., et al.: "Mutations of the p53 gene as a prognostic factor in aggressive B-cell lymphoma." N.Engl.J.Med.337. 529-534 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Uchida T., Kinoshita T., Nagai et al.H.: "Hypermethylation of the p15^<INK4B> gene in myelodysplastic syndromes." Blood. 90. 1403-1409 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakahara Y., Nagai H., Kinoshita T., et al.: "Mutational analysis of the PTEN/MMAC1 gene in non-Hodgkin's lymphoma." Leukemia. 12. 1277-1280 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tomita A., Watanabe T., Kinoshita T., et al.: "Truncated c-Myb expression in the human leukemia cell line TK-6." Leukemia. 12. 1422-1429 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Suzuki H., Aasano H., Kinoshita T., et al.: "Clonality analysis of refractory anemia with ring sideroblasts : simultaneous study of clonality and cytochemistry of bone marrow progenitors." Leukemia. 13. 130-134 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Isogai C., Murate T., Kinoshita T., et al.: "Analysis of bax protein in sphingosine-induced apoptosis in the human leukemic cell line TF1 and its bcl-2 transfectants." Experimental Hematology. 26. 1118-1125 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nagai, H., Kinoshita T., Suzuki H., et al.: "Identification and Mapping of Novel Tumor Suppressor Loci on 6p in Diffuse Large B-cell non-Hodgkin Lymphoma" Genes, Chromosomes & Cancer. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nagai H., Kinoshita T., Suzuki H., et al.: "Identification and Mapping of Novel Tumor Suppressor Loci on 6p in Diffuse B-cell non-Hodgkin Lymphoma" Genes,Chromosomes & Cancer. 発表予定.

    • Related Report
      1998 Annual Research Report
  • [Publications] Tomita A., Watanabe t., Kinoshita T., et al.: "Trncated c-Myb expression in the human leukemia cell line TK-6" Leukemia. 12. 1422-1429 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nakahara,Y.Nagai H., Kinoshita T., et al.: "Mutational analysisi of the PTEN/MMAC1 gene in non-Hodgkin's lymphoma" Leukemia. 12. 1277-1280 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Uchida T., Kinoshita T., Nagai H., et al.: "Hypermethylation of the p15^<INK4B> gene in myelodysplastic syndromes" Blood. 90. 1403-1409 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ichikawa A., Kinoshita T., Watanabe T., et al.: "Mutations of the p53 gene as a prognostic factor in aggressive B-cell lymphoma." N.Engl.J.Med.337. 529-534 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kurokawa T., Kinoshita T., Murate T., et al.: "Complementarity determining region-III is a useful molecular marker for the evaluation of minimal residual disease in mantle cell lymphoma." Br.J.Haematol.98. 408-412 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 木下朝博、永井宏和 他: "悪性リンパ腫の発症・進展と癌抑制遺伝子血液・腫瘍科" 科学評論社, 160-166 (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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