Dec 25, 2009

Complex landscapes of somatic rearrangement in human breast cancer genomes

Nature
Philip StephensMichael R Stratton

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.

  • References38
  • Citations363

Citations

Mentioned in this Paper

Genome
DNA Stability
Neoplasms
Thyroid Hormone Plasma Membrane Transport Defect
Autosome Abnormalities
Sequencing
Tandem
DNA Breaks
Sequence Determinations, DNA
Mammary Neoplasms, Human

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