AID produces DNA double-strand breaks in non-Ig genes and mature B cell lymphomas with reciprocal chromosome translocations

Mol Cell. 2009 Nov 25;36(4):631-41. doi: 10.1016/j.molcel.2009.11.007.


Cancer-initiating translocations such as those associated with lymphomas require the formation of paired DNA double-strand breaks (DSBs). Activation-induced cytidine deaminase (AID) produces widespread somatic mutation in mature B cells; however, the extent of "off-target" DSB formation and its role in translocation-associated malignancy is unknown. Here, we show that deregulated expression of AID causes widespread genome instability, which alone is insufficient to induce B cell lymphoma; transformation requires concomitant loss of the tumor suppressor p53. Mature B cell lymphomas arising as a result of deregulated AID expression are phenotypically diverse and harbor clonal reciprocal translocations involving a group of Immunoglobulin (Ig) and non-Ig genes that are direct targets of AID. This group includes miR-142, a previously unknown micro-RNA target that is translocated in human B cell malignancy. We conclude that AID produces DSBs throughout the genome, which can lead to lymphoma-associated chromosome translocations in mature B cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / enzymology
  • Cell Differentiation / genetics
  • Cells, Cultured
  • Chromosomal Instability / genetics
  • Chromosomes, Mammalian / genetics*
  • Cytidine Deaminase / metabolism*
  • DNA Breaks, Double-Stranded*
  • DNA Damage
  • Genes, Immunoglobulin / genetics*
  • Humans
  • Immunoglobulin Class Switching / genetics
  • Karyotyping
  • Lymphoma, B-Cell / enzymology*
  • Lymphoma, B-Cell / genetics*
  • Lymphoma, B-Cell / pathology
  • Mice
  • Mice, Transgenic
  • MicroRNAs / metabolism
  • Phenotype
  • Proto-Oncogene Proteins c-myc / genetics
  • Somatic Hypermutation, Immunoglobulin / genetics
  • Translocation, Genetic*
  • Tumor Suppressor Protein p53 / deficiency


  • MicroRNAs
  • Mirn142 microRNA, mouse
  • Proto-Oncogene Proteins c-myc
  • Tumor Suppressor Protein p53
  • AICDA (activation-induced cytidine deaminase)
  • Cytidine Deaminase