Chimeric IgH-TCR/ translocations in T lymphocytes mediated by RAG

Elsa Callén, Sam Bunting, Ching Yu Huang, Michael J. Difilippantonio, Nancy Wong, Bernard Khor, Grace Mahowald, Michael J. Kruhlak, Thomas Ried, Barry P. Sleckman, André Nussenzweig

Research output: Contribution to journalArticleResearchpeer-review

17 Citations (Scopus)


Translocations involving the T cell receptor alpha/delta (TCRα/δ) chain locus, which bring oncogenes in the proximity of the TCRα 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 TCRα/δ locus to a disperse region centromeric of the immunoglobulin heavy chain (IgH) locus. Aberrant VDJ joining accounts for TCRα/δ 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/ TCRα/δ fusions arise at a remarkably similar frequency as in human AT lymphocytes. Recombinase-activating gene (RAG) is responsible for both TCRα/δ 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. ©2009 Landes Bioscience.
Original languageEnglish
Pages (from-to)2408-2412
JournalCell Cycle
Issue number15
Publication statusPublished - 1 Aug 2009


  • ATM
  • T cell leukemia
  • Translocations
  • V(D)J recombination


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