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

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,...

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Bibliographic Details
Published in:	Nature (London) Vol. 464; no. 7291; pp. 999 - 1005
Main Authors:	Wilson, Richard K, Ding, Li, Ellis, Matthew J, Li, Shunqiang, Larson, David E, Chen, Ken, Wallis, John W, Harris, Christopher C, McLellan, Michael D, Fulton, Robert S, Fulton, Lucinda L, Abbott, Rachel M, Hoog, Jeremy, Dooling, David J, Koboldt, Daniel C, Schmidt, Heather, Kalicki, Joelle, Zhang, Qunyuan, Chen, Lei, Lin, Ling, Wendl, Michael C, McMichael, Joshua F, Magrini, Vincent J, Cook, Lisa, McGrath, Sean D, Vickery, Tammi L, Appelbaum, Elizabeth, DeSchryver, Katherine, Davies, Sherri, Guintoli, Therese, Lin, Li, Crowder, Robert, Tao, Yu, Snider, Jacqueline E, Smith, Scott M, Dukes, Adam F, Sanderson, Gabriel E, Pohl, Craig S, Delehaunty, Kim D, Fronick, Catrina C, Pape, Kimberley A, Reed, Jerry S, Robinson, Jody S, Hodges, Jennifer S, Schierding, William, Dees, Nathan D, Shen, Dong, Locke, Devin P, Wiechert, Madeline E, Eldred, James M, Peck, Josh B, Oberkfell, Benjamin J, Lolofie, Justin T, Du, Feiyu, Hawkins, Amy E, O’Laughlin, Michelle D, Bernard, Kelly E, Cunningham, Mark, Elliott, Glendoria, Mason, Mark D, Thompson Jr, Dominic M, Ivanovich, Jennifer L, Goodfellow, Paul J, Perou, Charles M, Weinstock, George M, Aft, Rebecca, Watson, Mark, Ley, Timothy J, Mardis, Elaine R
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 15-04-2010 Nature Publishing Group
Subjects:	631/67/322 631/67/69 692/699/67/1347 Adult alpha Catenin - genetics Brain Neoplasms - genetics Brain Neoplasms - secondary Breast Breast cancer Breast Neoplasms - genetics Breast Neoplasms - pathology Cancer Cancer therapies Chemotherapy Comparative analysis Deletion Deoxyribonucleic acid Development and progression Disease Progression DNA DNA Copy Number Variations - genetics DNA Mutational Analysis DNA repair DNA sequencing Enrichment Female Gene amplification Gene Frequency - genetics Gene mutations Genetic aspects Genetic testing Genetics Genome, Human - genetics Genomes Genomics Health aspects Humanities and Social Sciences Humans Metastasis Methods multidisciplinary Mutation Mutation - genetics Mutations Neoplasm Transplantation Nucleotide sequencing Risk factors Science Science (multidisciplinary) Translocation, Genetic - genetics Transplantation, Heterologous Tumors Tumours United States
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Summary:	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. Cancer progression genomics With the latest DNA sequencing technologies it is now possible to screen an entire genome for the genetic changes associated with tumour progression. This approach has been used to obtain complete sequences of four DNA samples from a 44-year-old African-American patient with basal-like breast cancer: the primary tumour, peripheral blood, a brain metastasis and a first-passage xenograft derived from the primary tumour. Mutational analysis suggests that the metastasis tumour specifically selects a subset of cells from the primary tumour that contain pre-existing mutations, and also develops a small number of de novo mutations. Massively parallel DNA sequencing allows entire genomes to be screened for genetic changes associated with tumour progression. Here, the genomes of four DNA samples from a 44-year-old African-American patient with basal-like breast cancer were analysed. The samples came from peripheral blood, the primary tumour, a brain metastasis and a xenograft derived from the primary tumour. The findings indicate that cells with a distinct subset of the primary tumour mutation might be selected during metastasis and xenografting.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work
ISSN:	0028-0836 1476-4687
DOI:	10.1038/nature08989