Complex landscapes of somatic rearrangement in human breast cancer genomes.

Stephens, Philip J., Mcbride, David J., Lin, Meng-lay, Varela, Ignacio, Pleasance, Erin D., Simpson, Jared T., Stebbings, Lucy A., Leroy, Catherine, Edkins, Sarah, Mudie, Laura J., Greenman, Christopher, Jia, Mingming, Latimer, Calli, Teague, Jon W., Lau, King Wai, Burton, John, Quail, Michael A., Swerdlow, Harold, Churcher, Carol, Natrajan, Rachael, Sieuwerts, Anieta M., Martens, John W. M., Silver, Daniel P., Langerød, Anita, Russnes, Hege E. G., Foekens, John A., Reis-filho, Jorge S., Van ’t Veer, Laura, Richardson, Andrea L., Børresen-Dale, Anne-Lise, Campbell, Peter J., Futreal, P. Andrew and Stratton, Michael R. (2009) Complex landscapes of somatic rearrangement in human breast cancer genomes. Nature, 462 (7276). pp. 1005-1010. ISSN 1476-4687

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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.

Item Type: Article
Faculty \ School: Faculty of Science > School of Computing Sciences

University of East Anglia > Faculty of Science > Research Groups > Computational Biology (subgroups are shown below) > Analysis and models of genomic variation
Faculty of Science > School of Biological Sciences
Depositing User: Christopher Greenman
Date Deposited: 22 Jun 2011 11:07
Last Modified: 21 Apr 2020 17:47
URI: https://ueaeprints.uea.ac.uk/id/eprint/30592
DOI: 10.1038/nature08645

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