Complex landscapes of somatic rearrangement in human breast cancer genomes

Philip J. Stephens, David J. McBride, Meng-Lay Lin, Ignacio Varela, Erin D. Pleasance, Jared T. Simpson, Lucy A. Stebbings, Catherine Leroy, Sarah Edkins, Laura J. Mudie, Chris D. Greenman, Mingming Jia, Calli Latimer, Jon W. Teague, King Wai Lau, John Burton, Michael A. Quail, Harold Swerdlow, Carol Churcher, Rachael NatrajanAnieta M. Sieuwerts, John W. M. Martens, Daniel P. Silver, Anita Langerød, Hege E. G. Russnes, John A. Foekens, Jorge S. Reis-Filho, Laura van 't Veer, Andrea L. Richardson, Anne-Lise Børresen-Dale, Peter J. Campbell, P. Andrew Futreal, Michael R. Stratton

Research output: Contribution to journalArticlepeer-review

707 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)1005-1010
Number of pages6
Issue number7276
Publication statusPublished - 24 Dec 2009

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