Chimeric IgH-TCR/translocations in T lymphocytes mediated by RAG
Chimeric IgH-TCR/translocations in T lymphocytes mediated by RAG
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DOI：
10.4161/cc.8.15.9085
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发表时间：
2009-08-01
期刊：
影响因子：
4.3
通讯作者：
Nussenzweig, Andre
中科院分区：
文献类型：
--
作者：
Callen, Elsa;Bunting, Sam;Nussenzweig, Andre
Translocations involving the T cell receptor alpha/delta (TCR alpha/delta) chain locus, which bring oncogenes in the proximity of the TCR alpha enhancer, are one of the hallmark features of human T cell malignancies from ataxia telangiectasia (AT) and non-AT patients. These lesions are frequently generated by the fusion of DNA breaks at the TCR alpha/delta locus to a disperse region centromeric of the immunoglobulin heavy chain (IgH) locus. Aberrant VDJ joining accounts for TCR alpha/delta associated DNA cleavage, but the molecular mechanism that leads to generation of the "oncogene partner" DNA break is unclear. Here we show that in ATM deficient primary mouse T cells, IgH/TCR alpha/delta fusions arise at a remarkably similar frequency as in human AT lymphocytes. Recombinase-activating gene (RAG) is responsible for both TCR alpha/delta as well as IgH associated breaks on chromosome 12 (Chr12), which are subject to varying degrees of chromosomal degradation. We suggest a new model for how oncogenic translocations can arise from two non-concerted physiological DSBs.
