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Nature:乳腺癌中的染色体重排情况

来源:生命经纬 2009-12-25 11:27

专题:Nature报道

几十年前人们就知道很多肿瘤包含基因组重排,但对它们的原因和影响却知之甚少。

现在,Stephens等人利用新的“paired-end”测序技术以高分辨率确定了人类乳腺癌中的染色体重排分布情况。他们发现的重排比以前识别出的更多,其中大部分是染色体内重排,而不是染色体间重排。顺接重复在一些乳腺癌中非常普遍,但在另一些中却基本没有,而且它们可能反映了一个新颖的“Mutator 表现型”。(生物谷Bioon.com)

生物谷推荐原始出处:

Nature 462, 1005-1010 (24 December 2009) | doi:10.1038/nature08645

Complex landscapes of somatic rearrangement in human breast cancer genomes

Philip J. Stephens1, David J. McBride1, Meng-Lay Lin1, Ignacio Varela1, Erin D. Pleasance1, Jared T. Simpson1, Lucy A. Stebbings1, Catherine Leroy1, Sarah Edkins1, Laura J. Mudie1, Chris D. Greenman1, Mingming Jia1, Calli Latimer1, Jon W. Teague1, King Wai Lau1, John Burton1, Michael A. Quail1, Harold Swerdlow1, Carol Churcher1, Rachael Natrajan2, Anieta M. Sieuwerts3, John W. M. Martens3, Daniel P. Silver4, Anita Langer?d5, Hege E. G. Russnes5, John A. Foekens3, Jorge S. Reis-Filho2, Laura van ’t Veer6, Andrea L. Richardson4,7, Anne-Lise B?rresen-Dale5,8, Peter J. Campbell1, P. Andrew Futreal1 & Michael R. Stratton1,9

1 Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK
2 Molecular Pathology Laboratory, The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK
3 Department of Medical Oncology, Josephine Nefkens Institute, Erasmus University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands
4 Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
5 Department of Genetics, Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0310 Oslo, Norway
6 The Netherlands Cancer Institute, 121 Plesmanlaan, 1066 CX Amsterdam, The Netherlands
7 Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
8 Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Montebello, 0310 Oslo, Norway
9 Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
Correspondence to: P. Andrew Futreal1Michael R. Stratton1,9 Correspondence and requests for materials should be addressed to M.R.S. or P.A.F.

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.

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