2003 Fiscal Year Final Research Report Summary
Roles of translocation junction genes for proliferation and differentiation of hemotolymphoid cell
| Project/Area Number |
14370312
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Aichi Cancer Center |
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Principal Investigator |
SETO Masao Aichi Cancer Center, Molecular Medicine, Chief, 遺伝子医療研究部, 部長 (80154665)
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| 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)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Lymphoma / T-cell lymphoma / MALT Lymphoma / API2-MALT1 / API2 / MALT1 / Tissue-FISH |
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| 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.
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[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)
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[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)
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[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)
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[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)
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[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)
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[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)
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[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)
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[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)
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[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)
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[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)
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[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)
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[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)
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