title: Genomic and transcriptional aberrations linked to breast cancer pathophysiologies.
abstract: 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.
authors.affiliation: Comprehensive Cancer Center, 2340 Sutter Street, University of California, San Francisco, San Francisco, California 94143.
authors.forename: Koei
authors.initials: K
authors.lastname: Chin
authors.forename: Sandy
authors.initials: S
authors.lastname: DeVries
authors.forename: Jane
authors.initials: J
authors.lastname: Fridlyand
authors.forename: Paul T
authors.initials: PT
authors.lastname: Spellman
authors.forename: Ritu
authors.initials: R
authors.lastname: Roydasgupta
authors.forename: Wen-Lin
authors.initials: WL
authors.lastname: Kuo
authors.forename: Anna
authors.initials: A
authors.lastname: Lapuk
authors.forename: Richard M
authors.initials: RM
authors.lastname: Neve
authors.forename: Zuwei
authors.initials: Z
authors.lastname: Qian
authors.forename: Tom
authors.initials: T
authors.lastname: Ryder
authors.forename: Fanqing
authors.initials: F
authors.lastname: Chen
authors.forename: Heidi
authors.initials: H
authors.lastname: Feiler
authors.forename: Taku
authors.initials: T
authors.lastname: Tokuyasu
authors.forename: Chris
authors.initials: C
authors.lastname: Kingsley
authors.forename: Shanaz
authors.initials: S
authors.lastname: Dairkee
authors.forename: Zhenhang
authors.initials: Z
authors.lastname: Meng
authors.forename: Karen
authors.initials: K
authors.lastname: Chew
authors.forename: Daniel
authors.initials: D
authors.lastname: Pinkel
authors.forename: Ajay
authors.initials: A
authors.lastname: Jain
authors.forename: Britt Marie
authors.initials: BM
authors.lastname: Ljung
authors.forename: Laura
authors.initials: L
authors.lastname: Esserman
authors.forename: Donna G
authors.initials: DG
authors.lastname: Albertson
authors.forename: Frederic M
authors.initials: FM
authors.lastname: Waldman
authors.forename: Joe W
authors.initials: JW
authors.lastname: Gray
mesh_terms: 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