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Cancer genomics

Translocation patterns revealed

Nature Reviews Genetics volume 12, page 741 (2011)Cite this article

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To induce a DSB at a specific locus and thus recapitulate the initiation of translocation, Klein et al. and Chiarle et al. used mouse B lymphocytes (both wild-type and AID−/−) with engineered I-SceI sites at either the immunoglobulin heavy chain (IgH) or Myc locus; these loci are common oncogenic translocation partners and hence important locations of physiological translocations. I-SceI sites were converted to DSBs by the action of the transduced yeast I-SceI endonuclease. Both teams carried out amplification and high-throughput sequencing of the induced rearrangements. This was possible because the sequence on one side of the engineered breakpoint is known. They identified hundreds of thousands of independent chromosomal translocation events in hundreds of millions of B lymphocytes.

Genome-wide analysis of translocation sites showed that most rearrangements occurred intrachromosomally, particularly within 350 kb of the induced breakpoint, suggesting that proximity of DSBs is a key determinant of translocation sites. Outside this proximal region, both teams found an enrichment of translocation events in genic regions. Intriguingly, this intrachromosomal and genic bias is also seen in the genomes of tumours.

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ORIGINAL RESEARCH PAPERS

  1. Klein, I. A. et al. Translocation-capture sequencing reveals the extent and nature of chromosomal rearrangements in B lymphocytes. Cell 147, 95–106 (2011)

    Article  CAS  PubMed  Google Scholar 

  2. Chiarle, R. et al. Genome-wide translocation sequencing reveals mechanisms of chromosome breaks and rearrangements in B cells. Cell 147, 107–119 (2011)

    Article  CAS  PubMed  Google Scholar 

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Authors
  1. Darren J. Burgess
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Burgess, D. Translocation patterns revealed. Nat Rev Genet 12, 741 (2011). https://doi.org/10.1038/nrg3090

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