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

Cancer Medicine

Inga Reynisdottir¹  Adalgeir Arason¹  Berglind O. Einarsdottir¹  Haukur Gunnarsson¹  Johan Staaf²  Johan Vallon-Christersson²  Goran Jonsson²  Markus Ringnér²  Bjarni A. Agnarsson¹  Kristrun Olafsdottir¹  Rainer Fagerholm⁴  Thorbjorg Einarsdottir¹  Gudrun Johannesdottir¹  Oskar Thor Johannsson³  Heli Nevanlinna⁴  Ake Borg² 

[1] Department of Pathology, Landspitali-University Hospital, Reykjavik, Iceland;Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden;Department of Oncology, Landspitali-University Hospital, Reykjavik, Iceland;Department of Obstetrics and Gynaecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland

关键词: 8p12‐p11 amplification;    ER positive;    luminal tumors;    prognosis;    tumor progression;    ZNF703;   

DOI  :  10.1002/cam4.88

来源: Wiley

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.