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

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.

SUBMITTER: Tsai AG

PROVIDER: S-EPMC2642632 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

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

Tsai Albert G AG Lu Haihui H Raghavan Sathees C SC Muschen Markus M Hsieh Chih-Lin CL Lieber Michael R MR

Cell 20081201 6

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, matur ...[more]

PMID: 19070581

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