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

Li Ding, Matthew J. Ellis, Shunqiang Li, David E. Larson, Ken Chen, John W. Wallis, Christopher C. Harris, Michael D. McLellan, Robert S. Fulton, Lucinda L. Fulton, Rachel M. Abbott, Jeremy Hoog, David J. Dooling, Daniel C. Koboldt, Heather Schmidt, Joelle Kalicki, Qunyuan Zhang, Lei Chen, Ling Lin, Michael C. Wendl, Joshua F. McMichael, Vincent J. Magrini, Lisa Cook, Sean D. McGrath, Tammi L. Vickery, Elizabeth Appelbaum, Katherine DeSchryver, Sherri Davies, Therese Guintoli, Li Lin, Robert Crowder, Yu Tao, Jacqueline E. Snider, Scott M. Smith, Adam F. Dukes, Gabriel E. Sanderson, Craig S. Pohl, Kim D. Delehaunty, Catrina C. Fronick, Kimberley A. Pape, Jerry S. Reed, Jody S. Robinson, Jennifer S. Hodges, William Schierding, Nathan D. Dees, Dong Shen, Devin P. Locke, Madeline E. Wiechert, James M. Eldred, Josh B. Peck, Benjamin J. Oberkfell, Justin T. Lolofie, Feiyu Du, Amy E. Hawkins, Michelle D. O’Laughlin, Kelly E. Bernard, Mark Cunningham, Glendoria Elliott, Mark D. Mason, Dominic M. Thompson, Jennifer L. Ivanovich, Paul J. Goodfellow, Charles M. Perou, George M. Weinstock, Rebecca Aft, Mark Watson, Timothy J. Ley, Richard K. Wilson () and Elaine R. Mardis
Additional contact information
Li Ding: The Genome Center at Washington University,
Matthew J. Ellis: Department of Medicine,
Shunqiang Li: Department of Medicine,
David E. Larson: The Genome Center at Washington University,
Ken Chen: The Genome Center at Washington University,
John W. Wallis: The Genome Center at Washington University,
Christopher C. Harris: The Genome Center at Washington University,
Michael D. McLellan: The Genome Center at Washington University,
Robert S. Fulton: The Genome Center at Washington University,
Lucinda L. Fulton: The Genome Center at Washington University,
Rachel M. Abbott: The Genome Center at Washington University,
Jeremy Hoog: Department of Medicine,
David J. Dooling: The Genome Center at Washington University,
Daniel C. Koboldt: The Genome Center at Washington University,
Heather Schmidt: The Genome Center at Washington University,
Joelle Kalicki: The Genome Center at Washington University,
Qunyuan Zhang: Department of Genetics,
Lei Chen: The Genome Center at Washington University,
Ling Lin: The Genome Center at Washington University,
Michael C. Wendl: The Genome Center at Washington University,
Joshua F. McMichael: The Genome Center at Washington University,
Vincent J. Magrini: The Genome Center at Washington University,
Lisa Cook: The Genome Center at Washington University,
Sean D. McGrath: The Genome Center at Washington University,
Tammi L. Vickery: The Genome Center at Washington University,
Elizabeth Appelbaum: The Genome Center at Washington University,
Katherine DeSchryver: Department of Medicine,
Sherri Davies: Department of Medicine,
Therese Guintoli: Department of Medicine,
Li Lin: Department of Medicine,
Robert Crowder: Department of Medicine,
Yu Tao: Division of Biostatistics,
Jacqueline E. Snider: Department of Medicine,
Scott M. Smith: The Genome Center at Washington University,
Adam F. Dukes: The Genome Center at Washington University,
Gabriel E. Sanderson: The Genome Center at Washington University,
Craig S. Pohl: The Genome Center at Washington University,
Kim D. Delehaunty: The Genome Center at Washington University,
Catrina C. Fronick: The Genome Center at Washington University,
Kimberley A. Pape: The Genome Center at Washington University,
Jerry S. Reed: The Genome Center at Washington University,
Jody S. Robinson: The Genome Center at Washington University,
Jennifer S. Hodges: The Genome Center at Washington University,
William Schierding: The Genome Center at Washington University,
Nathan D. Dees: The Genome Center at Washington University,
Dong Shen: The Genome Center at Washington University,
Devin P. Locke: The Genome Center at Washington University,
Madeline E. Wiechert: The Genome Center at Washington University,
James M. Eldred: The Genome Center at Washington University,
Josh B. Peck: The Genome Center at Washington University,
Benjamin J. Oberkfell: The Genome Center at Washington University,
Justin T. Lolofie: The Genome Center at Washington University,
Feiyu Du: The Genome Center at Washington University,
Amy E. Hawkins: The Genome Center at Washington University,
Michelle D. O’Laughlin: The Genome Center at Washington University,
Kelly E. Bernard: The Genome Center at Washington University,
Mark Cunningham: The Genome Center at Washington University,
Glendoria Elliott: The Genome Center at Washington University,
Mark D. Mason: The Genome Center at Washington University,
Dominic M. Thompson: Department of Surgery and the Young Women’s Breast Cancer Program,
Jennifer L. Ivanovich: Department of Surgery and the Young Women’s Breast Cancer Program,
Paul J. Goodfellow: Department of Surgery and the Young Women’s Breast Cancer Program,
Charles M. Perou: Washington University School of Medicine, St Louis, Missouri 63108, USA
George M. Weinstock: The Genome Center at Washington University,
Rebecca Aft: Department of Surgery and the Young Women’s Breast Cancer Program,
Mark Watson: Lineberger Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA
Timothy J. Ley: The Genome Center at Washington University,
Richard K. Wilson: The Genome Center at Washington University,
Elaine R. Mardis: The Genome Center at Washington University,

Nature, 2010, vol. 464, issue 7291, 999-1005

Abstract: Abstract 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.

Date: 2010
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DOI: 10.1038/nature08989

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