title: BCL6 breaks occur at different AID sequence motifs in Ig-BCL6 and non-Ig-BCL6 rearrangements.
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.
authors.affiliation: Norris Comprehensive Cancer Center, Department of Pathology, Biochemistry, and Molecular Biology, University of Southern California, Los Angeles, CA, USA.
authors.forename: Zhengfei
authors.initials: Z
authors.lastname: Lu
authors.forename: Albert G
authors.initials: AG
authors.lastname: Tsai
authors.forename: Takashi
authors.initials: T
authors.lastname: Akasaka
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ohno
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Jiang
authors.forename: Ari M
authors.initials: AM
authors.lastname: Melnick
authors.forename: Harvey A
authors.initials: HA
authors.lastname: Greisman
authors.forename: Michael R
authors.initials: MR
authors.lastname: Lieber
mesh_terms: D019457:Chromosome Breakage; D003564:Cytidine Deaminase / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics*; D015322:Gene Rearrangement, B-Lymphocyte / Q000235:genetics; D018858:Germinal Center / Q000473:pathology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000473:pathology; D054448:Precursor Cells, B-Lymphoid / Q000201:enzymology / Q000473:pathology; D051560:Proto-Oncogene Proteins c-bcl-6; D014178:Translocation, Genetic / Q000235:genetics*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; D051560:Proto-Oncogene Proteins c-bcl-6; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase