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, 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.
Ding
Li
L
The Genome Center at Washington University, St Louis, Missouri 63108, USA.
Ellis
Matthew J
MJ
Li
Shunqiang
S
Larson
David E
DE
Chen
Ken
K
Wallis
John W
JW
Harris
Christopher C
CC
McLellan
Michael D
MD
Fulton
Robert S
RS
Fulton
Lucinda L
LL
Abbott
Rachel M
RM
Hoog
Jeremy
J
Dooling
David J
DJ
Koboldt
Daniel C
DC
Schmidt
Heather
H
Kalicki
Joelle
J
Zhang
Qunyuan
Q
Chen
Lei
L
Lin
Ling
L
Wendl
Michael C
MC
McMichael
Joshua F
JF
Magrini
Vincent J
VJ
Cook
Lisa
L
McGrath
Sean D
SD
Vickery
Tammi L
TL
Appelbaum
Elizabeth
E
Deschryver
Katherine
K
Davies
Sherri
S
Guintoli
Therese
T
Lin
Li
L
Crowder
Robert
R
Tao
Yu
Y
Snider
Jacqueline E
JE
Smith
Scott M
SM
Dukes
Adam F
AF
Sanderson
Gabriel E
GE
Pohl
Craig S
CS
Delehaunty
Kim D
KD
Fronick
Catrina C
CC
Pape
Kimberley A
KA
Reed
Jerry S
JS
Robinson
Jody S
JS
Hodges
Jennifer S
JS
Schierding
William
W
Dees
Nathan D
ND
Shen
Dong
D
Locke
Devin P
DP
Wiechert
Madeline E
ME
Eldred
James M
JM
Peck
Josh B
JB
Oberkfell
Benjamin J
BJ
Lolofie
Justin T
JT
Du
Feiyu
F
Hawkins
Amy E
AE
O'Laughlin
Michelle D
MD
Bernard
Kelly E
KE
Cunningham
Mark
M
Elliott
Glendoria
G
Mason
Mark D
MD
Thompson
Dominic M
DM
Ivanovich
Jennifer L
JL
Goodfellow
Paul J
PJ
Perou
Charles M
CM
Weinstock
George M
GM
Aft
Rebecca
R
Watson
Mark
M
Ley
Timothy J
TJ
Wilson
Richard K
RK
Mardis
Elaine R
ER
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
C495273:CTNNA1 protein, human; D051178:alpha Catenin
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