title: Genome remodelling in a basal-like breast cancer metastasis and xenograft.
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.
authors.affiliation: The Genome Center at Washington University, St Louis, Missouri 63108, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Ellis
authors.forename: Shunqiang
authors.initials: S
authors.lastname: Li
authors.forename: David E
authors.initials: DE
authors.lastname: Larson
authors.forename: Ken
authors.initials: K
authors.lastname: Chen
authors.forename: John W
authors.initials: JW
authors.lastname: Wallis
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Harris
authors.forename: Michael D
authors.initials: MD
authors.lastname: McLellan
authors.forename: Robert S
authors.initials: RS
authors.lastname: Fulton
authors.forename: Lucinda L
authors.initials: LL
authors.lastname: Fulton
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Abbott
authors.forename: Jeremy
authors.initials: J
authors.lastname: Hoog
authors.forename: David J
authors.initials: DJ
authors.lastname: Dooling
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Koboldt
authors.forename: Heather
authors.initials: H
authors.lastname: Schmidt
authors.forename: Joelle
authors.initials: J
authors.lastname: Kalicki
authors.forename: Qunyuan
authors.initials: Q
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Ling
authors.initials: L
authors.lastname: Lin
authors.forename: Michael C
authors.initials: MC
authors.lastname: Wendl
authors.forename: Joshua F
authors.initials: JF
authors.lastname: McMichael
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Magrini
authors.forename: Lisa
authors.initials: L
authors.lastname: Cook
authors.forename: Sean D
authors.initials: SD
authors.lastname: McGrath
authors.forename: Tammi L
authors.initials: TL
authors.lastname: Vickery
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Appelbaum
authors.forename: Katherine
authors.initials: K
authors.lastname: Deschryver
authors.forename: Sherri
authors.initials: S
authors.lastname: Davies
authors.forename: Therese
authors.initials: T
authors.lastname: Guintoli
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.forename: Robert
authors.initials: R
authors.lastname: Crowder
authors.forename: Yu
authors.initials: Y
authors.lastname: Tao
authors.forename: Jacqueline E
authors.initials: JE
authors.lastname: Snider
authors.forename: Scott M
authors.initials: SM
authors.lastname: Smith
authors.forename: Adam F
authors.initials: AF
authors.lastname: Dukes
authors.forename: Gabriel E
authors.initials: GE
authors.lastname: Sanderson
authors.forename: Craig S
authors.initials: CS
authors.lastname: Pohl
authors.forename: Kim D
authors.initials: KD
authors.lastname: Delehaunty
authors.forename: Catrina C
authors.initials: CC
authors.lastname: Fronick
authors.forename: Kimberley A
authors.initials: KA
authors.lastname: Pape
authors.forename: Jerry S
authors.initials: JS
authors.lastname: Reed
authors.forename: Jody S
authors.initials: JS
authors.lastname: Robinson
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Hodges
authors.forename: William
authors.initials: W
authors.lastname: Schierding
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Dees
authors.forename: Dong
authors.initials: D
authors.lastname: Shen
authors.forename: Devin P
authors.initials: DP
authors.lastname: Locke
authors.forename: Madeline E
authors.initials: ME
authors.lastname: Wiechert
authors.forename: James M
authors.initials: JM
authors.lastname: Eldred
authors.forename: Josh B
authors.initials: JB
authors.lastname: Peck
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Oberkfell
authors.forename: Justin T
authors.initials: JT
authors.lastname: Lolofie
authors.forename: Feiyu
authors.initials: F
authors.lastname: Du
authors.forename: Amy E
authors.initials: AE
authors.lastname: Hawkins
authors.forename: Michelle D
authors.initials: MD
authors.lastname: O'Laughlin
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Bernard
authors.forename: Mark
authors.initials: M
authors.lastname: Cunningham
authors.forename: Glendoria
authors.initials: G
authors.lastname: Elliott
authors.forename: Mark D
authors.initials: MD
authors.lastname: Mason
authors.forename: Dominic M
authors.initials: DM
authors.lastname: Thompson
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Ivanovich
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Goodfellow
authors.forename: Charles M
authors.initials: CM
authors.lastname: Perou
authors.forename: George M
authors.initials: GM
authors.lastname: Weinstock
authors.forename: Rebecca
authors.initials: R
authors.lastname: Aft
authors.forename: Mark
authors.initials: M
authors.lastname: Watson
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Ley
authors.forename: Richard K
authors.initials: RK
authors.lastname: Wilson
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Mardis
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000235:genetics* / Q000556:secondary*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D056915:DNA Copy Number Variations / Q000235:genetics; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D015894:Genome, Human / Q000235:genetics*; D023281:Genomics; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009368:Neoplasm Transplantation; D014178:Translocation, Genetic / Q000235:genetics; D014183:Transplantation, Heterologous; D051178:alpha Catenin / Q000235:genetics
chemical_list: C495273:CTNNA1 protein, human; D051178:alpha Catenin
references.citation: Breast Cancer Res Treat. 2010 Jun;121(3):555-63
references.pmid: 19669408
references.citation: Nucleic Acids Res. 2003 Jul 1;31(13):3812-4
references.pmid: 12824425
references.citation: J Clin Oncol. 2003 Apr 15;21(8):1431-9
references.pmid: 12668651
references.citation: Science. 2006 Oct 13;314(5797):268-74
references.pmid: 16959974
references.citation: Cancer Res. 2008 Apr 15;68(8):2592-8
references.pmid: 18413727
references.citation: Genome Res. 2009 Sep;19(9):1639-45
references.pmid: 19541911
references.citation: J Clin Oncol. 2009 Mar 10;27(8):1160-7
references.pmid: 19204204
references.citation: Nat Genet. 2005 Jun;37(6):590-2
references.pmid: 15908952
references.citation: Nat Rev Cancer. 2008 Feb;8(2):83-93
references.pmid: 18094723
references.citation: Proc Natl Acad Sci U S A. 2004 Apr 6;101(14):4966-71
references.pmid: 15051869
references.citation: Science. 2003 May 9;300(5621):949
references.pmid: 12738854
references.citation: Nature. 2009 Oct 8;461(7265):809-13
references.pmid: 19812674
references.citation: Science. 2005 Aug 12;309(5737):1074-8
references.pmid: 16099986
references.citation: Nat Methods. 2009 Sep;6(9):677-81
references.pmid: 19668202
references.citation: Mol Cancer Res. 2006 Dec;4(12):935-43
references.pmid: 17189384
references.citation: Nature. 2010 Jan 14;463(7278):191-6
references.pmid: 20016485
references.citation: J Biol Chem. 2009 Aug 14;284(33):22048-22058
references.pmid: 19494114
references.citation: Genes Chromosomes Cancer. 2004 Oct;41(2):99-108
references.pmid: 15287022
references.citation: Am J Pathol. 2009 Oct;175(4):1662-74
references.pmid: 19745064
references.citation: Nature. 2010 Jan 14;463(7278):184-90
references.pmid: 20016488
references.citation: J Biol Chem. 2009 Jul 3;284(27):18252-9
references.pmid: 19458087
references.citation: Mol Cell Biol. 2003 Oct;23(20):7377-90
references.pmid: 14517305
references.citation: Genome Res. 2008 Nov;18(11):1851-8
references.pmid: 18714091
references.citation: N Engl J Med. 2009 Sep 10;361(11):1058-66
references.pmid: 19657110
references.citation: Science. 2008 Sep 12;321(5895):1499-502
references.pmid: 18787170
references.citation: Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9414-8
references.pmid: 19470474
references.citation: Nature. 2008 Nov 6;456(7218):66-72
references.pmid: 18987736
references.citation: Genes Chromosomes Cancer. 2003 Jun;37(2):132-40
references.pmid: 12696061
references.citation: JAMA. 2006 Jun 7;295(21):2492-502
references.pmid: 16757721
references.citation: Science. 2007 Nov 16;318(5853):1108-13
references.pmid: 17932254