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High expression of ZNF703 independent of amplification indicates worse prognosis in patients with luminal B breast cancer

  • Inga Reynisdottir
  • Adalgeir Arason
  • Berglind Einarsdottir
  • Haukur Gunnarsson
  • Johan Staaf
  • Johan Vallon-Christersson
  • Göran B Jönsson
  • Markus Ringnér
  • Bjarni Agnarsson
  • Kristrun Olafsdottir
  • Rainer Fagerholm
  • Thorbjorg Einarsdottir
  • Gudrun Johannesdottir
  • Oskar Thor Johannsson
  • Heli Nevanlinna
  • Åke Borg
  • Rosa Barkardottir
Publishing year: 2013
Language: English
Pages: 437-446
Publication/Series: Cancer Medicine
Volume: 2
Issue: 4
Document type: Journal article
Publisher: Wiley-Blackwell

Abstract english

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.


  • Cancer and Oncology
  • ZNF703
  • tumor progression
  • prognosis
  • luminal tumors
  • ER positive
  • 8p12-p11 amplification


  • ISSN: 2045-7634
Markus Ringnér
E-mail: markus [dot] ringner [at] biol [dot] lu [dot] se

Research engineer

Molecular Cell Biology


Sölvegatan 35, Lund