Genomic and transcriptional aberrations linked to breast cancer pathophysiologies.
This study explores the roles of genome copy number abnormalities (CNAs) in breast cancer pathophysiology by identifying associations between recurrent CNAs, gene expression, and clinical outcome in a set of aggressively treated early-stage breast tumors. It shows that the recurrent CNAs differ between tumor subtypes defined by expression pattern and that stratification of patients according to outcome can be improved by measuring both expression and copy number, especially high-level amplification. Sixty-six genes deregulated by the high-level amplifications are potential therapeutic targets. Nine of these (FGFR1, IKBKB, ERBB2, PROCC, ADAM9, FNTA, ACACA, PNMT, and NR1D1) are considered druggable. Low-level CNAs appear to contribute to cancer progression by altering RNA and cellular metabolism.
Chin
Koei
K
Comprehensive Cancer Center, 2340 Sutter Street, University of California, San Francisco, San Francisco, California 94143.
DeVries
Sandy
S
Fridlyand
Jane
J
Spellman
Paul T
PT
Roydasgupta
Ritu
R
Kuo
Wen-Lin
WL
Lapuk
Anna
A
Neve
Richard M
RM
Qian
Zuwei
Z
Ryder
Tom
T
Chen
Fanqing
F
Feiler
Heidi
H
Tokuyasu
Taku
T
Kingsley
Chris
C
Dairkee
Shanaz
S
Meng
Zhenhang
Z
Chew
Karen
K
Pinkel
Daniel
D
Jain
Ajay
A
Ljung
Britt Marie
BM
Esserman
Laura
L
Albertson
Donna G
DG
Waldman
Frederic M
FM
Gray
Joe W
JW
D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D002869:Chromosome Aberrations; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D014158:Transcription, Genetic