1. BCL6 breaks occur at different AID sequence motifs in Ig–BCL6 and non-Ig–BCL6 rearrangements
- Author
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Zhengfei Lu, Harvey A. Greisman, Hitoshi Ohno, Yanwen Jiang, Ari Melnick, Albert G. Tsai, Michael R. Lieber, and Takashi Akasaka
- Subjects
Lymphoma, B-Cell ,Immunology ,Biology ,Biochemistry ,Translocation, Genetic ,Recombination-activating gene ,immune system diseases ,Cytidine Deaminase ,hemic and lymphatic diseases ,Humans ,Gene Rearrangement, B-Lymphocyte ,Genetics ,Lymphoid Neoplasia ,Precursor Cells, B-Lymphoid ,Breakpoint ,Intron ,Chromosome Breakage ,Cell Biology ,Hematology ,Cytidine deaminase ,Germinal Center ,BCL6 ,Molecular biology ,DNA-Binding Proteins ,CpG site ,Proto-Oncogene Proteins c-bcl-6 ,Immunoglobulin heavy chain ,Chromosome breakage ,Immunoglobulin Heavy Chains - Abstract
BCL6 translocations are common in B-cell lymphomas and frequently have chromosomal breaks in immunoglobulin heavy chain (IgH) switch regions, suggesting that they occur during class-switch recombination. We analyze 120 BCL6 translocation breakpoints clustered in a 2156-bp segment of BCL6 intron 1, including 62 breakpoints (52%) joined to IgH, 12 (10%) joined to Ig light chains, and 46 (38%) joined to non-Ig partners. The BCL6 breaks in Ig-BCL6 translocations prefer known activation-induced cytosine deaminase (AID) hotspots such as WGCW and WRC (W = A/T, R = A/G), whereas BCL6 breaks in non-Ig rearrangements occur at CpG/CGC sites in addition to WGCW. Unlike previously identified CpG breaks in pro-B/pre-B-cell translocations, the BCL6 breaks do not show evidence of recombination activating gene or terminal deoxynucleotidyl transferase activity. Both WGCW/WRC and CpG/CGC breaks at BCL6 are most likely initiated by AID in germinal center B-cells, and their differential use suggests subtle mechanistic differences between Ig-BCL6 and non-Ig-BCL6 rearrangements.
- Published
- 2013