ZNF703 gene amplification at 8p12 specifies luminal B breast cancer

• Published in: EMBO molecular medicine Vol. 3; no. 3; pp. 153 - 166
• Main Authors: Sircoulomb, Fabrice, Nicolas, Nathalie, Ferrari, Anthony, Finetti, Pascal, Bekhouche, Ismahane, Rousselet, Estelle, Lonigro, Aurélie, Adélaïde, José, Baudelet, Emilie, Esteyriès, Séverine, Wicinski, Julien, Audebert, Stéphane, Charafe‐Jauffret, Emmanuelle, Jacquemier, Jocelyne, Lopez, Marc, Borg, Jean‐Paul, Sotiriou, Christos, Popovici, Cornel, Bertucci, François, Birnbaum, Daniel, Chaffanet, Max, Ginestier, Christophe
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2011; WILEY‐VCH Verlag; EMBO Press; Wiley Open Access; WILEY-VCH Verlag
• Subjects: 8p11 amplification; Biology; Breast cancer; Breast Neoplasms - genetics; Cancer; cancer stem cell; Cancer therapies; Carrier Proteins - genetics; Cell activation; Cell cycle; Cell Line; Cellular Biology; Chromosome 8; Copy number; E2F1 Transcription Factor - metabolism; Endocrine therapy; Female; Gene Amplification; Gene Expression; Gene regulation; Genomes; Humans; Life Sciences; luminal B; Lymphocytes B; Mass Spectrometry; Mass spectroscopy; Medical prognosis; Menopause; Proteins; Receptors, Estrogen - metabolism; Research Article; Signal transduction; Software; Stem cells; Tumorigenesis; Tumors; ZNF703; France; 8p11 amplification; breast cancer; cancer stem cell; luminal B; ZNF703
• ISSN: 1757-4676; 1757-4684
• DOI: 10.1002/emmm.201100121

Luminal B breast cancers represent a fraction of oestrogen receptor (ER)‐positive tumours associated with poor recurrence‐free and disease‐specific survival in all adjuvant systemic treatment categories including hormone therapy alone. Identification of specific signalling pathways driving luminal B biology is paramount to improve treatment. We have studied 100 luminal breast tumours by combined analysis of genome copy number aberrations and gene expression. We show that amplification of the ZNF703 gene, located in chromosomal region 8p12, preferentially occurs in luminal B tumours. We explored the functional role of ZNF703 in luminal B tumours by overexpressing ZNF703 in the MCF7 luminal cell line. Using mass spectrometry, we identified ZNF703 as a co‐factor of a nuclear complex comprising DCAF7, PHB2 and NCOR2. ZNF703 expression results in the activation of stem cell‐related gene expression leading to an increase in cancer stem cells. Moreover, we show that ZNF703 is implicated in the regulation of ER and E2F1 transcription factor. These findings point out the prominent role of ZNF703 in transcription modulation, stem cell regulation and luminal B oncogenesis. →See accompanying Closeup by Vessela Kristensen DOI https://doi.org/10.1002/emmm201100128