title: High expression of ZNF703 independent of amplification indicates worse prognosis in patients with luminal B breast cancer.
abstract: Amplification of 8p12-p11 is relatively common in breast cancer and several genes within the region have been suggested to affect breast tumor progression. The aim of the study was to map the amplified 8p12-p11 region in a large set of breast tumors in an effort to identify the genetic driver and to explore its impact on tumor progression and prognosis. Copy number alterations (CNAs) were mapped in 359 tumors, and gene expression data from 577 tumors (359 tumors included) were correlated with CNA, clinical-pathological factors, and protein expression (39 tumors). 8p12-p11 was amplified in 11.4% of tumors. The smallest region of amplification harbored one full-length gene, ZNF703. ZNF703 mRNA expression was significantly higher in estrogen receptor (ER)-positive than ER-negative tumors (P = 2 × 10(-16)), a reflection of high expression in luminal tumors. Forty-eight percent of tumors with ZNF703 amplification were luminal B tumors in which the best correlation between DNA copy number and mRNA was seen (P = 1.2 × 10(-7)) as well as correlation between mRNA and protein expression (P = 0.02). High ZNF703 mRNA correlated with poor survival in patients with ER-positive luminal B tumors (log rank P = 0.04). Furthermore, high ZNF703 mRNA expression correlated with poor outcome in patients with ZNF703 copy number neutral, ER-positive, luminal B tumors (log rank P = 0.004). The results support ZNF703 as the driver gene of the 8p12 amplification and suggest that independent of amplification, high expression of the gene affects prognosis in luminal B tumors.
authors.affiliation: Department of Pathology, Landspitali-University Hospital 101, Reykjavik, Iceland.
authors.forename: Inga
authors.initials: I
authors.lastname: Reynisdottir
authors.forename: Adalgeir
authors.initials: A
authors.lastname: Arason
authors.forename: Berglind O
authors.initials: BO
authors.lastname: Einarsdottir
authors.forename: Haukur
authors.initials: H
authors.lastname: Gunnarsson
authors.forename: Johan
authors.initials: J
authors.lastname: Staaf
authors.forename: Johan
authors.initials: J
authors.lastname: Vallon-Christersson
authors.forename: Goran
authors.initials: G
authors.lastname: Jonsson
authors.forename: Markus
authors.initials: M
authors.lastname: Ringnér
authors.forename: Bjarni A
authors.initials: BA
authors.lastname: Agnarsson
authors.forename: Kristrun
authors.initials: K
authors.lastname: Olafsdottir
authors.forename: Rainer
authors.initials: R
authors.lastname: Fagerholm
authors.forename: Thorbjorg
authors.initials: T
authors.lastname: Einarsdottir
authors.forename: Gudrun
authors.initials: G
authors.lastname: Johannesdottir
authors.forename: Oskar Thor
authors.initials: OT
authors.lastname: Johannsson
authors.forename: Heli
authors.initials: H
authors.lastname: Nevanlinna
authors.forename: Ake
authors.initials: A
authors.lastname: Borg
authors.forename: Rosa Bjork
authors.initials: RB
authors.lastname: Barkardottir
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8; D005260:Female; D005784:Gene Amplification; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D012333:RNA, Messenger; C541016:ZNF703 protein, human
keywords: 8p12-p11 amplification; ER positive; ZNF703; luminal tumors; prognosis; tumor progression