Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-59223

Wilkerson, P M; Dedes, K J; Wetterskog, D; Mackay, A; Lambros, M B; Mansour, M; Frankum, J; Lord, C J; Natrajan, R; Ashworth, A; Reis-Filho, J S (2011). Functional characterization of EMSY gene amplification in human cancers. Journal of Pathology, 225(1):29-42.

[img]Published Version
PDF - Registered users only
11MB

View at publisher

Abstract

The 11q13-q14 locus is frequently amplified in human cancers, with a complex structure harbouring multiple potential oncogenic drivers. The EMSY gene has been proposed as a driver of the third core of the 11q13-q14 amplicon. This gene encodes a protein reported to be a BRCA2-binding partner, which when over-expressed would lead to impairment of BRCA2 functions and could constitute a mechanism for BRCA2 inactivation in non-hereditary breast and ovarian cancers. We hypothesized that if EMSY 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-based 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 EMSY amplification and 18 without. EMSY amplification was shown to correlate with EMSY mRNA levels, although not all cell lines harbouring EMSY amplification displayed EMSY mRNA or protein over-expression. RNA interference-mediated silencing of EMSY did not lead to a reduction in cell viability in tumour models harbouring EMSY amplification. Cell lines with and without EMSY 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 EMSY is unlikely to be a driver of the 11q13-q14 amplicon and does not have a dominant role in modulating the response to agents targeting cells with defective homologous recombination.

Citations

7 citations in Web of Science®
7 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

2 downloads since deposited on 17 Feb 2012
0 downloads since 12 months

Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Gynecology
DDC:610 Medicine & health
Language:English
Date:2011
Deposited On:17 Feb 2012 13:04
Last Modified:30 Nov 2013 16:13
Publisher:Wiley-Blackwell
ISSN:0022-3417 (P) 1096-9896 (E)
Publisher DOI:10.1002/path.2944
PubMed ID:21735447

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page