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  • Oncogenomics
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Identification and validation of an ERBB2 gene expression signature in breast cancers

Abstract

ERBB2 is a transmembrane tyrosine kinase receptor encoded by a gene located in chromosome region 17q12. Overexpression of ERBB2, generally by way of gene amplification, plays a role in mammary oncogenesis. This alteration can be overcome by use of the humanized monoclonal antibody trastuzumab (Herceptin™). Accurate determination of ERBB2 status is required for appropriate use of this targeted therapy and is currently analysed by immunohistochemistry (IHC) on tissue sections and/or fluorescence in situ hybridisation (FISH) on interphase chromosomes. We have studied the gene expression profiles of a series of 213 breast tumours and 16 breast cancer cell lines with known ERBB2 status, using Ipsogen's DiscoveryChip microarrays with 9000 cDNAs. We have identified 36 genes and expressed sequence tags that were differentially expressed in tumours and in cell lines with and without ERBB2 protein overexpression. This ERBB2-specific gene expression signature (GES) contained 29 overexpressed genes including the ERBB2 gene itself, five genes located in its immediate vicinity on 17q12, non-17q genes such as GATA4 and eight downregulated genes including oestrogen receptor α (ER). Some correlations were validated at the protein level using IHC on tissue microarrays. The GES was able to distinguish ERBB2-negative and -positive cancer samples, as well as FISH-negative and FISH-positive ERBB2 2+ IHC samples.

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Acknowledgements

This article is dedicated to the memory of P Basset. We thank F Birg, G Houvenaegel, D Maraninchi and C Mawas for encouragements, and M Chaffanet, S Deraco, R Houlgatte, C Nguyen and R Tagett for help and discussions. This work was supported by Ipsogen, Institut Paoli-Calmettes, Inserm, Université de la Méditerranée, and grants from the ‘Association pour la Recherche sur le Cancer’, the ‘Ligue Nationale contre le Cancer’, the ‘Ministère de la Santé’ and the ‘Ministère de la Recherche’ (PHRC 2001 No 24-01 and 2002 No 24-04). C G is the recipient of a fellowship from the ‘Ministère de la Recherche’.

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Correspondence to Daniel Birnbaum.

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Bertucci, F., Borie, N., Ginestier, C. et al. Identification and validation of an ERBB2 gene expression signature in breast cancers. Oncogene 23, 2564–2575 (2004). https://doi.org/10.1038/sj.onc.1207361

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