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Identification of an AID-independent pathway for chromosomal translocations between the Igh switch region and Myc

Nature Immunology volume 5, pages 1117–1123 (2004)Cite this article

Abstract

Chromosomal translocations involving immunoglobulin heavy chain (Igh) switch regions and an oncogene such as Myc represent initiating events in the development of many B cell malignancies. These translocations are widely thought to result from aberrant class-switch recombination. To test this model, we measured translocations in mice deficient in activation-induced cytidine deaminase (AID) that lack class-switch recombination. We found that AID made no measurable contribution to the generation of initial translocations, indicating that the intrinsic fragility of the switch regions or a pathway unrelated to AID is responsible for these translocations. In contrast, the outgrowth of translocation-positive cells was dependent on AID, raising the possibility that AID is important in tumor progression, perhaps by virtue of its mutagenic properties.

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Figure 1: Generation and detection of translocations between the Igh S region and Myc during plasmacytomagenesis.
Figure 2: Dual effect of AID on translocations.
Figure 3: Detection of translocations between the Igh S region and Myc in Aicda+/+ and Aicda−/− mice.
Figure 4: Breakpoints of Igh-Myc translocations.

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Acknowledgements

We thank T. Honjo for AID-deficient mice; E. Corbett for help with cytospins; R. Herlands and J. Williams for help with microscopy; G. Tokmoulina for help with cell sorting; M. Shlomchik, members of his laboratory and members of the Schatz group for discussions; S. Fugmann for critically reading the manuscript; and the W.M. Keck Facility at Yale Medical School for DNA sequencing services. Supported by the Howard Hughes Medical Institute.

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  1. Howard Hughes Medical Institute, and Section of Immunobiology, Yale University School of Medicine, New Haven, 06520, Connecticut, USA

    Shyam Unniraman, Shaoming Zhou & David G Schatz

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  1. Shyam Unniraman
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Correspondence to David G Schatz.

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Supplementary Fig. 1

Sequence of translocation junctions. (PDF 60 kb)

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Unniraman, S., Zhou, S. & Schatz, D. Identification of an AID-independent pathway for chromosomal translocations between the Igh switch region and Myc. Nat Immunol 5, 1117–1123 (2004). https://doi.org/10.1038/ni1127

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