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ZNF703 gene amplification at 8p12 specifies luminal B breast cancer

Authors

  • Fabrice Sircoulomb,

    1. Laboratoire d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Inserm, U891, Institut Paoli-Calmettes, Marseille, France
    2. MaRS Centre Toronto Medical Discovery district, Toronto, Ontario, Canada
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  • Nathalie Nicolas,

    1. Laboratoire d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Inserm, U891, Institut Paoli-Calmettes, Marseille, France
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  • Anthony Ferrari,

    1. Laboratoire d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Inserm, U891, Institut Paoli-Calmettes, Marseille, France
    2. Present address: Fondation Synergie Lyon Cancer, Centre Léon Bérard, Lyon, France
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  • Pascal Finetti,

    1. Laboratoire d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Inserm, U891, Institut Paoli-Calmettes, Marseille, France
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  • Ismahane Bekhouche,

    1. Laboratoire d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Inserm, U891, Institut Paoli-Calmettes, Marseille, France
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  • Estelle Rousselet,

    1. Laboratoire d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Inserm, U891, Institut Paoli-Calmettes, Marseille, France
    2. Present address: Texas Tech University, Lubbock, Texas, USA
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  • Aurélie Lonigro,

    1. Laboratoire d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Inserm, U891, Institut Paoli-Calmettes, Marseille, France
    2. Present address: Faculté de Médecine, CRN2M, UMR6231, IFR Jean Roche, Secteur Nord, Université de la Méditerranée, Marseille, France
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  • José Adélaïde,

    1. Laboratoire d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Inserm, U891, Institut Paoli-Calmettes, Marseille, France
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  • Emilie Baudelet,

    1. Département de Pharmacologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes, Marseille, France
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  • Séverine Esteyriès,

    1. Laboratoire d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Inserm, U891, Institut Paoli-Calmettes, Marseille, France
    2. Present address: Unité de Pharmacologie Clinique Expérimentale et Thérapeutique, CHU La Timone, Marseille, France
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  • Julien Wicinski,

    1. Laboratoire d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Inserm, U891, Institut Paoli-Calmettes, Marseille, France
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  • Stéphane Audebert,

    1. Département de Pharmacologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes, Marseille, France
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  • Emmanuelle Charafe-Jauffret,

    1. Laboratoire d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Inserm, U891, Institut Paoli-Calmettes, Marseille, France
    2. Département de BioPathologie, Institut Paoli-Calmettes, Marseille, France
    3. Université de la Méditerranée, Marseille, France
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  • Jocelyne Jacquemier,

    1. Laboratoire d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Inserm, U891, Institut Paoli-Calmettes, Marseille, France
    2. Département de BioPathologie, Institut Paoli-Calmettes, Marseille, France
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  • Marc Lopez,

    1. Laboratoire d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Inserm, U891, Institut Paoli-Calmettes, Marseille, France
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  • Jean-Paul Borg,

    1. Département de Pharmacologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes, Marseille, France
    2. Université de la Méditerranée, Marseille, France
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  • Christos Sotiriou,

    1. Institut Jules Bordet, Bruxelles, Belgique
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  • Cornel Popovici,

    1. Laboratoire d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Inserm, U891, Institut Paoli-Calmettes, Marseille, France
    2. Université de la Méditerranée, Marseille, France
    3. Present address: Génétique Médicale, Hôpital de la Timone, Marseille, France
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  • François Bertucci,

    1. Laboratoire d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Inserm, U891, Institut Paoli-Calmettes, Marseille, France
    2. Université de la Méditerranée, Marseille, France
    3. Département d'Oncologie Médicale, Institut Paoli-Calmettes, Marseille, France
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  • Daniel Birnbaum,

    1. Laboratoire d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Inserm, U891, Institut Paoli-Calmettes, Marseille, France
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  • Max Chaffanet,

    Corresponding author
    1. Laboratoire d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Inserm, U891, Institut Paoli-Calmettes, Marseille, France
    • Tel: +33 4 91 22 34 77; Fax: +33 4 91 22 35 44
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    • Contributed equally.

  • Christophe Ginestier

    Corresponding author
    1. Laboratoire d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Inserm, U891, Institut Paoli-Calmettes, Marseille, France
    • Tel: +33 4 91 22 35 09; Fax: +33 4 91 22 35 44
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    • Contributed equally.

Errata

This article is corrected by:

  1. Errata: ZNF703 gene amplification at 8p12 specifies luminal B breast cancer Volume 3, Issue 3, Article first published online: 1 March 2011

Abstract

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 10.1002/emmm201100128

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