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Nature. 2009 Dec 24;462(7276):1005-10. doi: 10.1038/nature08645.

Complex landscapes of somatic rearrangement in human breast cancer genomes.

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  • 1Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.

Abstract

Multiple somatic rearrangements are often found in cancer genomes; however, the underlying processes of rearrangement and their contribution to cancer development are poorly characterized. Here we use a paired-end sequencing strategy to identify somatic rearrangements in breast cancer genomes. There are more rearrangements in some breast cancers than previously appreciated. Rearrangements are more frequent over gene footprints and most are intrachromosomal. Multiple rearrangement architectures are present, but tandem duplications are particularly common in some cancers, perhaps reflecting a specific defect in DNA maintenance. Short overlapping sequences at most rearrangement junctions indicate that these have been mediated by non-homologous end-joining DNA repair, although varying sequence patterns indicate that multiple processes of this type are operative. Several expressed in-frame fusion genes were identified but none was recurrent. The study provides a new perspective on cancer genomes, highlighting the diversity of somatic rearrangements and their potential contribution to cancer development.

PMID:
20033038
[PubMed - indexed for MEDLINE]
PMCID:
PMC3398135
Free PMC Article

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