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The <jats:italic>EMSY<\/jats:italic> gene has been proposed as a driver of the third core of the 11q13\u2010q14 amplicon. This gene encodes a protein reported to be a BRCA2\u2010binding partner, which when over\u2010expressed would lead to impairment of BRCA2 functions and could constitute a mechanism for BRCA2 inactivation in non\u2010hereditary breast and ovarian cancers. We hypothesized that if <jats:italic>EMSY<\/jats:italic> amplification abrogates BRCA2 functions, cells harbouring this aberration would be unable to elicit competent homologous recombination DNA repair and, therefore, may have increased sensitivity to genotoxic therapies and potent PARP inhibitors. Microarray\u2010based comparative genomic hybridization of cell lines from distinct tumour sites, including breast, ovary, pancreas, oesophagus, lung and the oral cavity, led to the identification of 10 cell lines with <jats:italic>EMSY<\/jats:italic> amplification and 18 without. <jats:italic>EMSY<\/jats:italic> amplification was shown to correlate with <jats:italic>EMSY<\/jats:italic> mRNA levels, although not all cell lines harbouring <jats:italic>EMSY<\/jats:italic> amplification displayed <jats:italic>EMSY<\/jats:italic> mRNA or protein over\u2010expression. RNA interference\u2010mediated silencing of <jats:italic>EMSY<\/jats:italic> did not lead to a reduction in cell viability in tumour models harbouring <jats:italic>EMSY<\/jats:italic> amplification. Cell lines with and without <jats:italic>EMSY<\/jats:italic> amplification displayed a similar ability to elicit RAD51 foci in response to DNA damaging agents, and similar sensitivity to cisplatin and olaparib. Taken together, this suggests that <jats:italic>EMSY<\/jats:italic> is unlikely to be a driver of the 11q13\u2010q14 amplicon and does not have a dominant role in modulating the response to agents targeting cells with defective homologous recombination. Copyright \u00a9 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.2944","type":"journal-article","created":{"date-parts":[[2011,5,24]],"date-time":"2011-05-24T04:15:39Z","timestamp":1306210539000},"page":"29-42","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Functional characterization of <i>EMSY<\/i> gene amplification in human cancers"],"prefix":"10.1002","volume":"225","author":[{"given":"Paul M","family":"Wilkerson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantin 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