EMSY links the BRCA2 pathway to sporadic breast and ovarian cancer

Hughes-Davies, L., Huntsman, D., Ruas, M., Fuks, F., Bye, J., Chin, S. F., Milner, J., Brown, L. A., Hsu, F., Gilks, B., Nielsen, T., Schulzer, M., Chia, S., Ragaz, J., Cahn, A., Linger, L., Ozdag, H., Cattaneo, E., Jordanova, E. S., Schuuring, E., Yu, D. S., Venkitaraman, A., Ponder, B., Doherty, A., Aparicio, S., Bentley, D., Theillet, C., Ponting, C. P., Caldas, C. and Kouzarides, T. (2003) EMSY links the BRCA2 pathway to sporadic breast and ovarian cancer. Cell, 115 (5). pp. 523-35. ISSN 0092-8674

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The BRCA2 gene is mutated in familial breast and ovarian cancer, and its product is implicated in DNA repair and transcriptional regulation. Here we identify a protein, EMSY, which binds BRCA2 within a region (exon 3) deleted in cancer. EMSY is capable of silencing the activation potential of BRCA2 exon 3, associates with chromatin regulators HP1beta and BS69, and localizes to sites of repair following DNA damage. EMSY maps to chromosome 11q13.5, a region known to be involved in breast and ovarian cancer. We show that the EMSY gene is amplified almost exclusively in sporadic breast cancer (13%) and higher-grade ovarian cancer (17%). In addition, EMSY amplification is associated with worse survival, particularly in node-negative breast cancer, suggesting that it may be of prognostic value. The remarkable clinical overlap between sporadic EMSY amplification and familial BRCA2 deletion implicates a BRCA2 pathway in sporadic breast and ovarian cancer.

Item Type: Article
Additional Information: 0092-8674 Journal Article GDSC102
Keywords: BRCA2 Protein/deficiency/*genetics Base Sequence/genetics Breast Neoplasms/*genetics/metabolism Carcinoma/*genetics/metabolism Carrier Proteins/genetics Chromosomal Proteins, Non-Histone/genetics Chromosomes, Human, Pair 11/genetics DNA, Complementary/analysis/genetics Exons/genetics Female Gene Amplification/genetics Gene Silencing/physiology Genes, Regulator/genetics Genetic Predisposition to Disease/genetics Human Molecular Sequence Data Ovarian Neoplasms/*genetics/metabolism Phylogeny Plant Proteins/genetics Prognosis Protein Structure, Tertiary/genetics Repressor Proteins/genetics/*isolation & purification Signal Transduction Support, Non-U.S. Gov't
Schools and Departments: School of Life Sciences
Depositing User: Gee Wheatley
Date Deposited: 26 Mar 2007
Last Modified: 30 Nov 2012 16:51
URI: http://srodev.sussex.ac.uk/id/eprint/1019
Google Scholar:232 Citations
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