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 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 WendlJoshua F. McMichael, Vincent J. Magrini, Lisa Cook, Sean D. McGrath, Tammi L. Vickery, Elizabeth Appelbaum, Katherine Deschryver, Sherri Davies, Therese Guintoli, Li Lim, 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. Oĝlaughlin, 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 Ley, Richard K. Wilson, Elaine R. Mardis

Research output: Contribution to journalArticlepeer-review

907 Scopus citations

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.

Original languageEnglish
Pages (from-to)999-1005
Number of pages7
JournalNature
Volume464
Issue number7291
DOIs
StatePublished - Apr 15 2010

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