Human chromosomal translocations at CpG sites and a theoretical basis for their lineage and stage specificity

Cell. 2008 Dec 12;135(6):1130-42. doi: 10.1016/j.cell.2008.10.035.


We have assembled, annotated, and analyzed a database of over 1700 breakpoints from the most common chromosomal rearrangements in human leukemias and lymphomas. Using this database, we show that although the CpG dinucleotide constitutes only 1% of the human genome, it accounts for 40%-70% of breakpoints at pro-B/pre-B stage translocation regions-specifically, those near the bcl-2, bcl-1, and E2A genes. We do not observe CpG hotspots in rearrangements involving lymphoid-myeloid progenitors, mature B cells, or T cells. The stage specificity, lineage specificity, CpG targeting, and unique breakpoint distributions at these cluster regions may be explained by a lesion-specific double-strand breakage mechanism involving the RAG complex acting at AID-deaminated methyl-CpGs.

MeSH terms

  • B-Lymphocytes / metabolism*
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Chromosome Breakage
  • CpG Islands*
  • Cytidine Deaminase / metabolism
  • DNA Breaks, Double-Stranded
  • Genes, bcl-1
  • Genes, bcl-2
  • Homeodomain Proteins / metabolism
  • Humans
  • Leukemia, Lymphoid / genetics*
  • Leukemia, Lymphoid / metabolism
  • Translocation, Genetic*


  • Basic Helix-Loop-Helix Transcription Factors
  • Homeodomain Proteins
  • TCF3 protein, human
  • RAG-1 protein
  • AICDA (activation-induced cytidine deaminase)
  • Cytidine Deaminase