| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1998: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Research Abstract |
Chromosomal translocation involving the immunoglobulin heavy chain (lgH) gene at band 14q32.3 and its partner genes are closely associated with both the pathogenesis and clinical characteristics of B-cell malignancies. To define the actual incidence of 14q32.3 translocation with specific oncogene loci, we analyzed 173 patients with B-cell non-Hodgkin's lymphoma (NHL) by double-color fluorescence in situ hybridization (DC-FISH). DC-FISH using the lgH gene (14q32.3) in combination with c-MYC (8q24.1), BCL1(11q13.3), BCL2(18q21.3), BCL6(3q27), and PAX-5(9p13) gene probes detected lgH translocations in 70 (40.5%) of 173 patients. The partner genes involved in lgH translocation were identified 56 (80%) of 70 patients : a fusion of the lgH gene and oncogene probes were detected in 52 of 56 patients, particularly on interphase nuclei of 29 patients, in whom cytogenetic analysis was not informative. The most common partner gene was BCL2 in 19 patients (11% of total patients), followed by BCL1 in 11 (6%), c-MYC in 7 (4%), and PAX-5 in 2 (1%). In the remaining 4 patients the partners were 19q13 (BCL3), 6p25 (MUM1/IRF4), 1q36, and chromosome 8 in one each. Double translocation of the lgH gene was found in 3 patients. In all of them one of the partners of lgH translocation was c-MYC, and the other partner was BCL1, BCL2, and BCL6 gene, respectively, suggesting the multistep process of the lgH gene involvement implicated in the pathogenesis and progression of B-NHL. Furthermore, we cloned MALT1 gene in a patient with MALT lymphoma, and established a FISH method to detect the specific translocation of t(11 ; 18) using YAC clonesw. The t(11 ; 18) was detected in 4 of 39 patients with B-NHL and one of 12 patient with primary macroglobulinemia. Interphase FISH with lymphoma-specific translocation probes warrants establishing a novel classification and predicting outcome of patients with B-NHL.
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