ABSTRACT Overexpression of the receptor tyrosine kinase ERBB2 (also known as HER2) occurs in around 15% of breast cancers and is driven by amplification of the _ERBB2_ gene. _ERBB2_

amplification is a marker of poor prognosis, and although anti-ERBB2-targeted therapies have shown significant clinical benefit, _de novo_ and acquired resistance remains an important

problem. Genomic profiling has demonstrated that ERBB2+ve breast cancers are distinguished from ER+ve and ‘triple-negative’ breast cancers by harbouring not only the _ERBB2_ amplification on

17q12, but also a number of co-amplified genes on 17q12 and amplification events on other chromosomes. Some of these genes may have important roles in influencing clinical outcome, and

are truly addicted to the _ERBB2_ oncogene at the mRNA level and display a heterogeneous set of additional genetic dependencies. These include an addiction to the transcription factor gene

_TFAP2C_ when it is amplified and overexpressed, suggesting that _TFAP2C_ represents a genetic dependency in some ERBB2+ve breast cancer cells. Access through your institution Buy or

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COMPLEX REARRANGEMENTS FUEL ER+ AND HER2+ BREAST TUMOURS Article Open access 08 January 2025 IDENTIFICATION OF PUTATIVE ACTIONABLE ALTERATIONS IN CLINICALLY RELEVANT GENES IN BREAST CANCER

Article 28 August 2021 THE ROLE OF HER2 AND HER3 IN HER2-AMPLIFIED CANCERS BEYOND BREAST CANCERS Article Open access 27 April 2021 ACCESSION CODES ACCESSIONS GENBANK/EMBL/DDBJ * E-TABM-543

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Download references ACKNOWLEDGEMENTS This work was supported by grants from Cancer Research UK, AACR as part of the Stand Up To Cancer Breast Cancer Dream Team Initiative, and Breakthrough

Breast Cancer. Dr Kai-Keen Shiu is an Avon Clinical Fellow. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research,

London, UK K-K Shiu, D Wetterskog, A Mackay, R Natrajan, M Lambros, D Sims, I Bajrami, R Brough, J Frankum, R Sharpe, N Turner, J S Reis-Filho, C J Lord & A Ashworth * Department of

Biomedical Sciences and Human Oncology, University of Turin, Turin, Italy C Marchio * Department of Pathology, Academic Medical Centre, Amsterdam, The Netherlands H Horlings, F Reyal & M

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Integrative molecular and functional profiling of _ERBB2-_amplified breast cancers identifies new genetic dependencies. _Oncogene_ 33, 619–631 (2014). https://doi.org/10.1038/onc.2012.625

Download citation * Received: 29 May 2012 * Revised: 04 November 2012 * Accepted: 14 November 2012 * Published: 21 January 2013 * Issue Date: 30 January 2014 * DOI:

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currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * HER2-positive breast cancer * microarrays * gene

expression * comparative genomic hybridization * siRNA screens * TFAP2C