TitleBCL6 breaks occur at different AID sequence motifs in Ig-BCL6 and non-Ig-BCL6 rearrangements.
Publication TypeJournal Article
Year of Publication2013
AuthorsLu, Zhengfei, Tsai Albert G., Akasaka Takashi, Ohno Hitoshi, Jiang Yanwen, Melnick Ari M., Greisman Harvey A., and Lieber Michael R.
JournalBlood
Volume121
Issue22
Pagination4551-4
Date Published2013 May 30
ISSN1528-0020
KeywordsChromosome Breakage, Cytidine Deaminase, DNA-Binding Proteins, Gene Rearrangement, B-Lymphocyte, Germinal Center, Humans, Immunoglobulin Heavy Chains, Lymphoma, B-Cell, Precursor Cells, B-Lymphoid, Proto-Oncogene Proteins c-bcl-6, Translocation, Genetic
Abstract

<p>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.</p>

DOI10.1182/blood-2012-10-464958
Alternate JournalBlood
PubMed ID23476051
PubMed Central IDPMC3668488
Grant ListR01 GM056984 / GM / NIGMS NIH HHS / United States