Document Detail


Integrative molecular and functional profiling of ERBB2-amplified breast cancers identifies new genetic dependencies.
MedLine Citation:
PMID:  23334330     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 could represent genetic dependencies in ERBB2+ve cancers and therefore potential therapeutic targets. Here, we describe an integrated genomic, gene expression and functional analysis to determine whether the genes present within amplicons are critical for the survival of ERBB2+ve breast tumour cells. We show that only a fraction of the ERBB2-amplified breast tumour lines 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.Oncogene advance online publication, 21 January 2013; doi:10.1038/onc.2012.625.
Authors:
K-K Shiu; D Wetterskog; A Mackay; R Natrajan; M Lambros; D Sims; I Bajrami; R Brough; J Frankum; R Sharpe; C Marchio; H Horlings; F Reyal; M van der Vijver; N Turner; J S Reis-Filho; C J Lord; A Ashworth
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-21
Journal Detail:
Title:  Oncogene     Volume:  -     ISSN:  1476-5594     ISO Abbreviation:  Oncogene     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, UK.
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