Complex landscapes of somatic rearrangement in human breast cancer genomes

被引：632

作者：

Stephens, Philip J. ^{[1
]}

McBride, David J. ^{[1
]}

Lin, Meng-Lay ^{[1
]}

Varela, Ignacio ^{[1
]}

Pleasance, Erin D. ^{[1
]}

Simpson, Jared T. ^{[1
]}

Stebbings, Lucy A. ^{[1
]}

Leroy, Catherine ^{[1
]}

Edkins, Sarah ^{[1
]}

Mudie, Laura J. ^{[1
]}

Greenman, Chris D. ^{[1
]}

Jia, Mingming ^{[1
]}

Latimer, Calli ^{[1
]}

Teague, Jon W. ^{[1
]}

Lau, King Wai ^{[1
]}

Burton, John ^{[1
]}

Quail, Michael A. ^{[1
]}

Swerdlow, Harold ^{[1
]}

Churcher, Carol ^{[1
]}

Natrajan, Rachael ^{[2
]}

Sieuwerts, Anieta M. ^{[3
]}

Martens, John W. M. ^{[3
]}

Silver, Daniel P. ^{[4
]}

Langerod, Anita ^{[5
]}

Russnes, Hege E. G. ^{[5
]}

Foekens, John A. ^{[3
]}

Reis-Filho, Jorge S. ^{[2
]}

van't Veer, Laura ^{[6
]}

Richardson, Andrea L. ^{[4
,7
]}

Borresen-Dale, Anne-Lise ^{[5
,8
]}

Campbell, Peter J.

Futreal, P. Andrew ^{[1
]}

Stratton, Michael R. ^{[1
,9
]}

机构：

[1] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England

[2] Inst Canc Res, Breakthrough Breast Canc Res Ctr, Mol Pathol Lab, London SW3 6JB, England

[3] Erasmus Univ, Med Ctr, Josephine Nefkens Inst, Dept Med Oncol, NL-3000 CA Rotterdam, Netherlands

[4] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA

[5] Oslo Univ Hosp, Norwegian Radium Hosp, Dept Genet, N-0310 Oslo, Norway

[6] Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands

[7] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

[8] Oslo Univ Hosp Radiumhosp, Inst Canc Res, Dept Genet, N-0310 Oslo, Norway

[9] Inst Canc Res, Sutton SM2 5NG, Surrey, England

来源：

NATURE | 2009年 / 462卷 / 7276期

基金：

英国惠康基金;

关键词：

TANDEM DUPLICATION; MYELOID-LEUKEMIA; COPY NUMBER; FUSION GENE; PATTERNS; TRANSLOCATIONS; IDENTIFICATION; ABERRATIONS; ETV6-NTRK3; MUTATION;

D O I：

10.1038/nature08645

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：1005 / U60

页数：8

共 37 条

[1] Translocation and gross deletion breakpolints in human inherited disease and cancer I: Nucleotide composition and recomblination-assocliated motifs [J].

Abeysinghe, SS ;

Chuzhanova, N ;

Krawczak, M ;

Ball, EV ;

Cooper, DN .

HUMAN MUTATION, 2003, 22 (03) :229-244

[2] The MLL partial tandem duplication in acute myeloid leukaemia [J].

Basecke, Jorg ;

Whelan, Jarrett T. ;

Griesinger, Frank ;

Bertrand, Fred E. .

BRITISH JOURNAL OF HAEMATOLOGY, 2006, 135 (04) :438-449

[3] Distinct patterns of DNA copy number alteration are associated with different clinicopathological features and gene-expression subtypes of breast cancer [J].

Bergamaschi, Anna ;

Kim, Young H. ;

Wang, Pei ;

Sorlie, Therese ;

Hernandez-Boussard, Tina ;

Lonning, Per E. ;

Tibshirani, Robert ;

Borresen-Dale, Anne-Lise ;

Pollack, Jonathan R. .

GENES CHROMOSOMES & CANCER, 2006, 45 (11) :1033-1040

[4] Architectures of somatic genomic rearrangement in human cancer amplicons at sequence-level resolution [J].

Bignell, Graham R. ;

Santarius, Thomas ;

Pole, Jessica C. M. ;

Butler, Adam P. ;

Perry, Janet ;

Pleasance, Erin ;

Greenman, Chris ;

Menzies, Andrew ;

Taylor, Sheila ;

Edkins, Sarah ;

Campbell, Peter ;

Quail, Michael ;

Plumb, Bob ;

Matthews, Lucy ;

Mclay, Kirsten ;

Edwards, Paul A. W. ;

Rogers, Jane ;

Wooster, Richard ;

Futreal, P. Andrew ;

Stratton, Michael R. .

GENOME RESEARCH, 2007, 17 (09) :1296-1303

[5] Replication licensing and cancer - a fatal entanglement? [J].

Blow, J. Julian ;

Gillespie, Peter J. .

NATURE REVIEWS CANCER, 2008, 8 (10) :799-806

[6] ETV6: A versatile player in leukemogenesis [J].

Bohlander, SK .

SEMINARS IN CANCER BIOLOGY, 2005, 15 (03) :162-174

[7] Identification of somatically acquired rearrangements in cancer using genome-wide massively parallel paired-end sequencing [J].

Campbell, Peter J. ;

Stephens, Philip J. ;

Pleasance, Erin D. ;

O'Meara, Sarah ;

Li, Heng ;

Santarius, Thomas ;

Stebbings, Lucy A. ;

Leroy, Catherine ;

Edkins, Sarah ;

Hardy, Claire ;

Teague, Jon W. ;

Menzies, Andrew ;

Goodhead, Ian ;

Turner, Daniel J. ;

Clee, Christopher M. ;

Quail, Michael A. ;

Cox, Antony ;

Brown, Clive ;

Durbin, Richard ;

Hurles, Matthew E. ;

Edwards, Paul A. W. ;

Bignell, Graham R. ;

Stratton, Michael R. ;

Futreal, P. Andrew .

NATURE GENETICS, 2008, 40 (06) :722-729

[8] Genomic and transcriptional aberrations linked to breast cancer pathophysiologies [J].

Chin, Koei ;

DeVries, Sandy ;

Fridlyand, Jane ;

Spellman, Paul T. ;

Roydasgupta, Ritu ;

Kuo, Wen-Lin ;

Lapuk, Anna ;

Neve, Richard M. ;

Qian, Zuwei ;

Ryder, Tom ;

Chen, Fanqing ;

Feiler, Heidi ;

Tokuyasu, Taku ;

Kingsley, Chris ;

Dairkee, Shanaz ;

Meng, Zhenhang ;

Chew, Karen ;

Pinkel, Daniel ;

Jain, Ajay ;

Ljung, Britt Marie ;

Esserman, Laura ;

Albertson, Donna G. ;

Waldman, Frederic M. ;

Gray, Joe W. .

CANCER CELL, 2006, 10 (06) :529-541

[9] Comprehensive genomic characterization defines human glioblastoma genes and core pathways [J].

Chin, L. ;

Meyerson, M. ;

Aldape, K. ;

Bigner, D. ;

Mikkelsen, T. ;

VandenBerg, S. ;

Kahn, A. ;

Penny, R. ;

Ferguson, M. L. ;

Gerhard, D. S. ;

Getz, G. ;

Brennan, C. ;

Taylor, B. S. ;

Winckler, W. ;

Park, P. ;

Ladanyi, M. ;

Hoadley, K. A. ;

Verhaak, R. G. W. ;

Hayes, D. N. ;

Spellman, Paul T. ;

Absher, D. ;

Weir, B. A. ;

Ding, L. ;

Wheeler, D. ;

Lawrence, M. S. ;

Cibulskis, K. ;

Mardis, E. ;

Zhang, Jinghui ;

Wilson, R. K. ;

Donehower, L. ;

Wheeler, D. A. ;

Purdom, E. ;

Wallis, J. ;

Laird, P. W. ;

Herman, J. G. ;

Schuebel, K. E. ;

Weisenberger, D. J. ;

Baylin, S. B. ;

Schultz, N. ;

Yao, Jun ;

Wiedemeyer, R. ;

Weinstein, J. ;

Sander, C. ;

Gibbs, R. A. ;

Gray, J. ;

Kucherlapati, R. ;

Lander, E. S. ;

Myers, R. M. ;

Perou, C. M. ;

McLendon, Roger .

NATURE, 2008, 455 (7216) :1061-1068

[10] A census of human cancer genes [J].

Futreal, PA ;

Coin, L ;

Marshall, M ;

Down, T ;

Hubbard, T ;

Wooster, R ;

Rahman, N ;

Stratton, MR .

NATURE REVIEWS CANCER, 2004, 4 (03) :177-183

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