| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
135 leukemia and lymphoma patients were precisely analyzed by FISH method. We found a new mechanism for gene amplification, chromosome segmental jumping translocation(SJT), in which chromosomal segment translocates to several portions of chromosomal end. Seven more regions, 1q22-23, 2q22-25, 3q24-27, 5q22-32, 7q23-25, 16q22-23, 20q21-22, were identified by present SKY-FISH analysis, in addition to eight SJT regions(8q24, 9q34, 11q13, 11q22-23, 14q32-34, 21q22, 22q11). Common regions within four SJTs were identified by FISH using about 10 cosmid and YAC probes. 8q24SJT and 11q13SJT contained MYC and Cyclin D gene, respectively. Highly expressed gene, locating within a SJT will be candidate genes for associating with malignant transformation. MYC gene expressed in all lymphoma with 8q24SJT, but not in some leukemias. Cyclin D1 gene expressed in all leukemias and lymphomas. Twenty metaphases obtained from a myeloid leukemia cell line, OHN-GM, were microdissected and extracted DNAs were amplified by DOP-PCR.These purified DNAs were used as FISH probes and FISH was applied to two patients for following observation of prognosis on interphase nucleus. DNA fragments microdissected from SJT were hybridized with c-DNA libraries established from same cell line. So far, 5-8 positive clones were identified. A SJT seemed to be a common unit for formation of human chromosome in chromosomal evolution and after neoplastic transformation it acquires transpotition to several chromosomal ends. Also SJT are found in chemical-and radiation-induced leukemias. SJT will be a target region for etiological agents.
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