Genome remodelling in a basal-like breast cancer metastasis and xenograft

被引：937

作者：

Ding, Li ^{[1
,2
]}

Ellis, Matthew J. ^{[3
,4
]}

Li, Shunqiang ^{[3
]}

Larson, David E. ^{[1
]}

Chen, Ken ^{[1
]}

Wallis, Johnw. ^{[1
,2
]}

Harris, Christopher C. ^{[1
]}

McLellan, Michael D. ^{[1
]}

Fulton, Robert S. ^{[1
,2
]}

Fulton, Lucinda L. ^{[1
,2
]}

Abbott, Rachel M. ^{[1
]}

Hoog, Jeremy ^{[3
]}

Dooling, David J. ^{[1
,2
]}

Koboldt, Daniel C. ^{[1
]}

Schmidt, Heather ^{[1
]}

Kalicki, Joelle ^{[1
]}

Zhang, Qunyuan ^{[2
,5
]}

Chen, Lei ^{[1
]}

Lin, Ling ^{[1
]}

Wendl, Michael C. ^{[1
,2
]}

McMichael, Joshua F. ^{[1
]}

Magrini, Vincent J. ^{[1
,2
]}

Cook, Lisa ^{[1
]}

McGrath, Sean D. ^{[1
]}

Vickery, Tammi L. ^{[1
]}

Appelbaum, Elizabeth ^{[1
]}

DeSchryver, Katherine ^{[3
]}

Davies, Sherri ^{[3
]}

Guintoli, Therese ^{[3
]}

Lin, Li ^{[3
]}

Crowder, Robert ^{[3
]}

Tao, Yu ^{[6
]}

Snider, Jacqueline E. ^{[3
]}

Smith, Scott M. ^{[1
]}

Dukes, Adam F. ^{[1
]}

Sanderson, Gabriel E. ^{[1
]}

Pohl, Craig S. ^{[1
]}

Delehaunty, Kim D. ^{[1
]}

Fronick, Catrina C. ^{[1
]}

Pape, Kimberley A. ^{[1
]}

Reed, Jerry S. ^{[1
]}

Robinson, Jody S. ^{[1
]}

Hodges, Jennifer S. ^{[1
]}

Schierding, William ^{[1
]}

Dees, Nathan D. ^{[1
]}

Shen, Dong ^{[1
]}

Locke, Devin P. ^{[1
]}

Wiechert, Madeline E. ^{[1
]}

Eldred, James M. ^{[1
]}

Peck, Josh B. ^{[1
]}

机构：

[1] Washington Univ, Genome Ctr, Sch Med, St Louis, MO 63108 USA

[2] Washington Univ, Dept Genet, Sch Med, St Louis, MO 63108 USA

[3] Washington Univ, Dept Med, Sch Med, St Louis, MO 63108 USA

[4] Washington Univ, Siteman Canc Ctr, Sch Med, St Louis, MO 63108 USA

[5] Washington Univ, Div Stat Genom, Sch Med, St Louis, MO 63108 USA

[6] Washington Univ, Div Biostat, Sch Med, St Louis, MO 63108 USA

[7] Washington Univ, Dept Surg, Sch Med, St Louis, MO 63108 USA

[8] Washington Univ, Young Womens Breast Canc Program, Sch Med, St Louis, MO 63108 USA

[9] Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO 63108 USA

[10] Univ N Carolina, Lineberger Canc Ctr, Dept Genet, Chapel Hill, NC 27599 USA

来源：

NATURE | 2010年 / 464卷 / 7291期

关键词：

MYELOID-LEUKEMIA GENOME; COLORECTAL CANCERS; SOMATIC MUTATIONS; TUMOR-SUPPRESSOR; LUNG-CANCER; DIFFERENTIATION; RESOLUTION; SUBTYPES; TAZ;

D O I：

10.1038/nature08989

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：

Massively parallel DNA sequencing technologies provide an unprecedented ability to screen entire genomes for genetic changes associated with tumour progression. Here we describe the genomic analyses of four DNA samples from an African-American patient with basal-like breast cancer: peripheral blood, the primary tumour, a brain metastasis and a xenograft derived from the primary tumour. The metastasis contained two de novo mutations and a large deletion not present in the primary tumour, and was significantly enriched for 20 shared mutations. The xenograft retained all primary tumour mutations and displayed a mutation enrichment pattern that resembled the metastasis. Two overlapping large deletions, encompassing CTNNA1, were present in all three tumour samples. The differential mutation frequencies and structural variation patterns in metastasis and xenograft compared with the primary tumour indicate that secondary tumours may arise from a minority of cells within the primary tumour.

引用

页码：999 / 1005

页数：7

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