| Title | BCL6 breaks occur at different AID sequence motifs in Ig-BCL6 and non-Ig-BCL6 rearrangements. |
| Publication Type | Journal Article |
| Year of Publication | 2013 |
| Authors | Lu, Zhengfei, Tsai Albert G., Akasaka Takashi, Ohno Hitoshi, Jiang Yanwen, Melnick Ari M., Greisman Harvey A., and Lieber Michael R. |
| Journal | Blood |
| Volume | 121 |
| Issue | 22 |
| Pagination | 4551-4 |
| Date Published | 2013 May 30 |
| ISSN | 1528-0020 |
| Keywords | Chromosome 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> |
| DOI | 10.1182/blood-2012-10-464958 |
| Alternate Journal | Blood |
| PubMed ID | 23476051 |
| PubMed Central ID | PMC3668488 |
| Grant List | R01 GM056984 / GM / NIGMS NIH HHS / United States |