THE T(14,18) CHROMOSOME TRANSLOCATIONS INVOLVED IN B-CELL NEOPLASMS RESULT FROM MISTAKES IN VDJ JOINING
THE T(14,18) CHROMOSOME TRANSLOCATIONS INVOLVED IN B-CELL NEOPLASMS RESULT FROM MISTAKES IN VDJ JOINING
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DOI：
10.1126/science.3929382
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发表时间：
1985-01-01
期刊：
影响因子：
56.9
通讯作者：
CROCE, CM
中科院分区：
文献类型：
--
作者：
TSUJIMOTO, Y;GORHAM, J;CROCE, CM
在本研究中，分析了一名前 B 细胞白血病患者和四名携带 t(14;18) 染色体易位的滤泡性淋巴瘤患者 14q+ 染色体上 14 号和 18 号染色体之间的连接序列。在每种情况下，18 号染色体的相关片段均已与 14 号染色体上的免疫球蛋白重链连接片段 (JH) 重组。14 号染色体上的重组位点位于靠近相关 JH 片段的 5'' 端，其中多样性 (D) 区域在产生活性重链基因时与 JH 片段重新排列。由于在连接位点观察到了外来核苷酸（N区），并且在靠近断点的18号染色体上检测到了特定的信号样序列，因此得出结论，t（14;18）染色体易位是在分化前B细胞阶段VDJ连接过程中的错误结果。假定的重组酶将两条不同染色体上分离的 DNA 片段连接起来，而不是连接同一条染色体上分离的片段，从而导致相关 B 细胞中发生 t(14;18) 染色体易位。
In this study, the joining sequences between chromosomes 14 and 18 on the 14q+ chromosomes of a patient with pre-B-cell leukemia and four patients with follicular lymphoma carrying a t(14;18) chromosome translocation were analyzed. In each case, the involved segment of chromosome 18 has recombined with the immunoglobulin heavy chain joining segment (JH) on chromosome 14. The sites of the recombination on chromosome 14 are located close to the 5'' end of the involved JH segment, where the diversity (D) regions are rearranged with the JH segments in the production of active heavy-chain genes. As extraneous nucleotides (N regions) were observed at joining sites and specific signal-like sequences were detected on chromosome 18 in close proximity to the breakpoints, it is concluded that the t(14;18) chromosome translocation is the result of a mistake during the process of VDJ joining at the pre-B cell stage of differentiation. The putative recombinase joins separated DNA segments on two different chromosomes instead of joining separated segments on the same chromosome, causing a t(14;18) chromosome translocation in the involved B cells.