1. Human chromosomal translocations at CpG sites and a theoretical basis for their lineage and stage specificity.
- Author
-
Tsai AG, Lu H, Raghavan SC, Muschen M, Hsieh CL, and Lieber MR
- Subjects
- Basic Helix-Loop-Helix Transcription Factors genetics, Chromosome Breakage, Cytidine Deaminase metabolism, DNA Breaks, Double-Stranded, Genes, bcl-1, Genes, bcl-2, Homeodomain Proteins metabolism, Humans, Leukemia, Lymphoid metabolism, B-Lymphocytes metabolism, CpG Islands, Leukemia, Lymphoid genetics, Translocation, Genetic
- Abstract
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.
- Published
- 2008
- Full Text
- View/download PDF