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Roles of translocation junction genes for proliferation and differentiation of hemotolymphoid cell

Research Project

Project/Area Number 14370312
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionAichi Cancer Center

Principal Investigator

SETO Masao  Aichi Cancer Center, Molecular Medicine, Chief, 遺伝子医療研究部, 部長 (80154665)

Co-Investigator(Kenkyū-buntansha) TSUZUKI Shinobu  Aichi Cancer Center, Molecular Medicine, Princpal Investigator, 遺伝子医療研究部, 主任研究員 (00342965)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2003: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 2002: ¥8,500,000 (Direct Cost: ¥8,500,000)
KeywordsLymphoma / T-cell lymphoma / MALT Lymphoma / API2-MALT1 / API2 / MALT1 / Tissue-FISH / 染色体転座 / ゲノム / 転座関連遺伝子 / T細胞リンパ腫 / T / NKリンパ腫
Research Abstract

The aim of the study is to identify genes that are involved in proliferation, differentiation and apoptosis for hematolymphoid cells and establish molecular markers useful for diagnosis and therapy. We have analyzed T-cell lymphoma breakpoint of chromosome 6q21 and identified TCBA1 (T-cell breakpoint cluster target 1). Its function on lymphomagenesis and cell differentiation remains to be explored. Mucosa-associated lymphoid tissue (MALT) lymphoma arises with chronic inflammation caused by H.pylori (gastric MALT lymphoma) or autoimmune diseases. Therefore, tumor cells are mixed with variable number of inflammatory cells.
In an attempt to analyze heterogeneity of MALT lymphoma, we measured API2-MALT1 chimeric mRNA copy number by REAL-Time PCR and tumor cell ratio by IgVH genomic sequence. As a result, API2-MALT1 copy number per tumor cell was found to vary as much as 100 times among the patients. This indicates that the heterogeneity of MALT lymphoma may be reflected by the amount of tumor cell and also by API2-MLAT1 chimeric mRNA copy number. MALT lymphoma without API2-MALT1 chimeric mRNA is also an important disease category to be explored. We are applying Tissue FISH method to this problem. Function of the concogenic gene is an important issue. Retroviral vector is being used and in combination with stem cell transplantation, in vivo function of API2-MALT1 is being studied.

Report

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

    (51 results)

All Other

All Publications (51 results)

  • [Publications] Yamaguchi, M.1他: "De nove CD5+ diffuse large B-cell lymphoma : a clinicopathologic study of 109 patients."Blood. 99. 1-7 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tagawa, H.他: "Molecular cytogenetic analysis of the breakpoint region at 6q21-22 in T-cell lymphoma/leukemia cell lines."Genes Chromosomes Cancer. 34. 175-185 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakamura, T.他: "Clinicopathologic Comparison between the API2-L4ALT1 Chimeric Transcript-positive and negative Gastric Low-grade B-Cell Lymphoma of Mucosa-associated Lymphoid Tissue Type."Jpn J Cancer Res.. 93. 677-684 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ito, M.他: "MUMI / IRF4 Expression Is an Unfavorable Prognostic Factor in B-Cell Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lyinphoma (SLL)."Jpn J Cancer Res.. 93. 677-684 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ando, T.他: "Fuzzy Neural Network applied to gene expression profiling for prognosis of diffuse large B-cell lymphoma."Jpn J Cancer Res.. 93. 685-694 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Seto, M.: "Molecular mechanisms of lymphomagenesis through transcriptional disregulation by chromosome translocation."Int J Hematol.. 1. 323-326 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nomura, K.他: "Detection of t(11;18)(q21;q21) in marginal zone lymphoma of mucosa-associated lymphocytic tissue type on paraffin-embedded tissue sections by using fluorescence in situ hybridization."Cancer Genet Cytogenet.. 140. 49-54 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ando, T.他: "Multiple fuzzy neural network system for outcome prediction and classification of 220 lymphoma patients on the basis of molecular profiling."Cancer Sci.. 94. 906-913 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sivasundram, K.他: "Mutational analysis of the ST7 gene in human myeloid tumor cell lines."Oncology Reports. 10. 1737-1739 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Izumiyama, K.他: "Stability and subcellular localization of API2-MALT1 chimeric protein involved in t(11;18)(q21;q21) MALT lymphoma."Oncogene. 22. 8085-8092 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakamura, T.他: "Gastric low-grade B-cell MALT lymphoma : treatment, response, and genetic alteration."J Gastroenterol.. 38. 921-929 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suguro-Katayama, M.他: "Heterogeneous copy numbers of API2-MALT1 chimeric transcripts in mucosa-associated lymphoid tissue lymphoma."Leukemia. 17. 2508-2512 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Karnan, S.他: "Analysis of Chromosomal Imbalances in de novo CD5-Positive Diffuse Large B-cell Lymphoma Detected by Comparative Genomic Hybridization."Genes Chromosomes Cancer. 39. 77-81 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsuo, K.他: "Lack of association between DNA base excision repair gene XRCC1 G1n399Arg polymorphism and risk of malignant lymphoma in Japan."Cancer Genetics and Cytogenetics. 149. 77-80 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tagawa, H.他: "MASL1, a candidate oncogene found in amplification at 8p23.1, is translocated in immunoblastic B-cell lymphoma cell line OCI-LY8."Oncogene. 23. 2576-2581 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ota, A.他: "Identification and Characterization of A Novel Gene, Cl3orf25, as A Target for 13q31-q32 Amplification in Malignant Lymphoma."Cancer Res.. 64. 3087-3095 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hosokawa, Y.他: "Anti-apoptotic function of API2-MALT1 fusion protein involved in t(11;14)(q21;q21) MALT lymphoma."Cancer Res.. 64. 3452-3457 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamaguchi, M., Seto, M., Okamoto, M., Ichinohasama, R., Nakamura, N., Yoshino, T., Suzumiya, J., Murase, T., Miura, I., Akasaka, T., Tamaru, H., Suzuki, R., Kagami, Y., Hirano, M., Morishima, Y., Ueda, R., Shiku, H., Nakamura, S.: "De nove CD5^+ diffuse large B-cell lymphoma : a clinicopathologic study of 109 patients."Blood. 99. 1-7 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tagawa, H., Miura, I., Suzuki, R., Suzuki, H., Hosokawa, Y., Seto, M.: "Molecular cytogenetic analysis of the breakpoint region at 6q21-22 in T-cell lymphoma/leukemia cell lines."Genes Chromosomes Cancer. 34. 175-185 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakamura, T., Nakamura, S., Yokoi, T., Suzuki, H., Ohashi, K.Seto, M.: "Clinicopathologic Comparison between the API2-MALT1 Chimeric Transcript-positive and -negative Gastric Low-grade B-Cell Lymphoma of Mucosa-associated Lymphoid Tissue Type."Jpn J Cancer res.. 93. 677-684 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ito, M., Iida, S., Inagaki, H., Tsuboi, K., Komatsu, H., Yamaguchi, M., Nakamura, N., Suzuki, R., Seto, M., Nakamura, S., Morishima Y., Ueda, R.: "MUM1/IRF4 Expression Is an Unfavorable Prognostic Factor in B-Cell Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)."Jpn J Cancer res.. 93. 685-694 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ando, T., Suguro, M., Hanai, T., Kobayashi, T., Honda, H., Seto, M.: "Fuzzy Neural Network applied to gene expression profiling for prognosis of diffuse large B-cell lymphoma."Jpn J Cancer res.. 93. 1207-1212 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Seto, M.: "Molecular mechanisms of lymphomagenesis through transcriptional disregulation by chromosome translocation."Int J Hematol.. 1. 323-326 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nomura, K., Yoshino, T., Nakamura, S., Akano, Y., Tagawa, H., Nishida, K., Seto, M., Nakamura, S., Ueda, R., Yamagishi, H., Taniwaki, M.: "Detection of t(11;18)(q21;q21) in marginal zone lymphoma of mucosa-associated lymphocytic tissue type on paraffin-embedded tissue sections by using fluorescence in situ hybridization."Cancer Genet Cytogenet.. 140. 49-54 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ando, T., Suguro, M., Kobayashi, T., Seto, M., Honda, H.: "Multiple fuzzy neural network system for outcome prediction and classification of 220 lymphoma patients on the basis of molecular profiling."Cancer Sci.. 94. 906-913 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sivasundram, K., Suzuki, H., Seto, M., Hosokawa, Y.: "Mutational analysis of the ST7 gene in human myeloid tumor cell lines."Oncology Reports. 10. 1737-1739 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Izumiyama, K., Nakagawa, M., Yonezumi, M., Kasugai, Y., Suzuki, R., Suzuki, H., Tsuzuki, S., Hosokawa, Y., Asaka, M., Seto, M.: "Stability and subcellular localization of API2-MALT1 chimeric protein involved in t(11;18)(q21;q21) MALT lymphoma."Oncogene. 22. 8085-8092 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakamura, T., Inagaki, H., Seto M., Nakamura, S.: "Gastric low-grade B-cell MALT lymphoma : treatment, response, and genetic alteration."J Gastroenterol.. 38. 921-929 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suguro-Katayama, M, Suzuki, R., Kasugai, Y., Nakamura, T., Suzuki, H., Hosokawa, Y., Shiku, H., Nakamura, S., Seto, M.: "Heterogeneous copy numbers of API2-MALT1 chimeric transcripts in mucosa-associated lymphoid tissue lymphoma."Leukemia. 17. 2508-2512 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Karnan, S., Tagawa, H., Suzuki, R., Suguro, M., Yamaguchi, M., Okamoto, M., Morishima, Y., Nakamura, S., Seto, M.: "Analysis of Chromosomal Imbalances in de novo CD5-Positive Diffuse Large B-cell Lymphoma Detected by Comparative Genomic Hybridization."Genes Chromosomes Cancer. 39. 77-81 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsuo, K., Hamajima, N., Suzuki, R., Andoh, S., Nakamura, S., Seto, M., Morishima, Y., Tajima, K.: "Lack Of association between DNA base excision repair gene XRCC1 Gln399Arg polymorphism and risk of malignant lymphoma in Japan."Cancer Genetics and Cytogenetics. 149. 77-80 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tagawa, H., Karnan, S., Kasugai, Y., Tuzuki, S., Suzuki R., Hosokawa, Y., Seto, M.: "MASL1, a candidate oncogene found in amplification at 8p23.1, is translocated in immunoblastic B-cell lymphoma cell line OCI-LY8."Oncogene. 23. 2576-2581 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ota, A., Tagawa, H., Karnan, S., Suzuki, Y., Karpas, S., Kira, S., Yoshida, Y., Seto, M.: "Identification and Characterization of A Novel Gene, C13orf25, as A Target for 13q31-q32 Amplification in Malignant Lymphoma"Cancer Res.. 64. 3084-3095 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hosokawa, Y., Suzuki, H., Suzuki, Y., Takahashi, R., Seto, M.: "Anti-apoptotic function of API2-MALT1 fusion protein involved in t(11;14)(q21;q21) MALT lymphoma"Cancer Res.. 64. 3452-3457 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nomura, K: "Detection of t(11;18)(q21;q21) in marginal zone lymphoma of mucosa-associated lymphocytic tissue type on paraffin-embedded tissue sections by using fluorescence in situ hybridization."Cancer Genet Cytogenet. 140. 49-54 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ando, T: "Multiple fuzzy neural network system for outcome prediction and classification of 220 lymphoma patients on the basis of molecular profiling."Cancer Sci. 94. 906-913 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sivasundram, K: "Mutational analysis of the ST7 gene in human myeloid tumor cell lines."Oncology Reports. 10. 1737-1739 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Izumiyama, K: "Stability and subcellular localization of API2-MALT1 chimeric protein involved in t(11;18)(q21;q21) MALT lymphoma."Oncogene. 22. 8085-8092 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakamura, T: "Gastric low-grade B-cell MALT lymphoma : treatment, response, and genetic alteration."J Gastroenterol. 38. 921-929 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Suguro-Katayama: "Heterogeneous copy numbers of API2-MALT1 chimeric transcripts in mucosa-associated lymphoid tissue lymphoma."Leukemia. 17. 2508-2512 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Karnan, S: "Analysis of Chromosomal Imbalances in de novo CD5-Positive Diffuse Large B-cell Lymphoma Detected by Comparative Genomic Hybridization."Genes Chromosomes Cancer. 39. 77-81 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Matsuo, K: "Lack Of association between DNA base excision repair gene XRCC1 Gln399 Arg polymorphism and risk of malignant lymphoma in Japan."Cancer Genetics and Cytogenetics. 149. 77-80 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tagawa, H: "MASL1,a candidate oncogene found in amplification at 8p23.1,is translocated in immunoblastic B-cell lymphoma cell line OCI-LY8."Oncogene. in press.

    • Related Report
      2003 Annual Research Report
  • [Publications] Hosokawa, Y: "Anti-apoptotic function of API2-MALT1 fusion protein involved in t(11;14)(q21;q21) MALT lymphoma."Cancer Res. in press.

    • Related Report
      2003 Annual Research Report
  • [Publications] Ota, A: "Identification and Characterization of A Novel Gene, C13orf25,as A Target for 13q31-q32 Amplification in Malignant Lymphoma."Cancer res. in press.

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamaguchi, M. 他: "De novo CD5+ diffuse large B-cell lymphoma : a clinicopathologic study of 109"Blood. 99. 815-821 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tagawa H. 他: "Molecular cytogenetic analysis of the breakpoint region at 6q21-22 in cell"Genes Chromosomes Cancer. 34. 175-185 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakamura T. 他: "Clinicopathologic Colmparison between the AP12-MALTI Chimeric Transcript-positive"Jpn. J. Cancer Res. 93. 677-684 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ito, M. 他: "MUM1/IRF4 Expression Is an Unfavorable Prognostic Factor in B-Cell Chr"Jpn J Cancer. 93. 685-694 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ando T. 他: "Fuzzy Neural Network Applied to Gene Expression Profiling for Predicting"Jpn J Cancer Res. 93. 1207-1212 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nomura, K. 他: "Detection of t(11;18)(q21;q21) in marginal zone lymphoma of mucosa-associ"Cancer Genet. Cytogenet. 140. 49-54 (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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