Abstract:
:Previous studies have implicated activation-induced cytidine deaminase (AID) in B-cell translocations but have failed to identify any association between their chromosomal breakpoints and known AID target sequences. Analysis of 56 unclustered IgH-CCND1 translocations in mantle cell lymphoma across the ~ 344-kb bcl-1 breakpoint locus demonstrates that half of the CCND1 breaks are near CpG dinucleotides. Most of these CpG breaks are at CGC motifs, and half of the remaining breaks are near WGCW, both known AID targets. These findings provide the strongest evidence to date that AID initiates chromosomal breaks in translocations that occur in human bone marrow B-cell progenitors. We also identify WGCW breaks at the MYC locus in Burkitt lymphoma translocations and murine IgH-MYC translocations, both of which arise in mature germinal center B cells. Finally, we propose a developmental model to explain the transition from CpG breaks in early human B-cell progenitors to WGCW breaks in later stage B cells.
journal_name
Bloodjournal_title
Bloodauthors
Greisman HA,Lu Z,Tsai AG,Greiner TC,Yi HS,Lieber MRdoi
10.1182/blood-2012-02-412791subject
Has Abstractpub_date
2012-10-04 00:00:00pages
2864-7issue
14eissn
0006-4971issn
1528-0020pii
blood-2012-02-412791journal_volume
120pub_type
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