EMSY Links the BRCA2 Pathway to Sporadic Breast and Ovarian Cancer

Abstract

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.

Keywords

BiologyBRCA2 ProteinOvarian cancerBreast cancerExonCancer researchGene silencingGeneChromatinCancerGeneticsMutationGermline mutation

MeSH Terms

BRCA2 ProteinBase SequenceBreast NeoplasmsCarcinomaCarrier ProteinsCell Cycle ProteinsChromobox Protein Homolog 5Chromosomal ProteinsNon-HistoneChromosomesHumanPair 11Co-Repressor ProteinsDNAComplementaryDNA-Binding ProteinsExonsFemaleGene AmplificationGene SilencingGenesRegulatorGenetic Predisposition to DiseaseHumansMolecular Sequence DataNeoplasm ProteinsNuclear ProteinsOvarian NeoplasmsPhylogenyPlant ProteinsPrognosisProtein StructureTertiaryRepressor ProteinsSignal Transduction

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Publication Info

Year: 2003
Type: article
Volume: 115
Issue: 5
Pages: 523-535
Citations: 417
Access: Closed

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APA Style

                            
                                
                                    Luke Hughes‐Davies, 
                                
                                    David G. Huntsman, 
                                
                                    Margarida Ruas
                                
                                et al.
                            
                            (2003). 
                            EMSY Links the BRCA2 Pathway to Sporadic Breast and Ovarian Cancer. 
                            Cell
                            , 115
                            (5)
                            , 523-535.
                            https://doi.org/10.1016/s0092-8674(03)00930-9
                        

Identifiers

DOI: 10.1016/s0092-8674(03)00930-9
PMID: 14651845

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Data completeness: 90%

EMSY Links the BRCA2 Pathway to Sporadic Breast and Ovarian Cancer

Abstract

Keywords

MeSH Terms

Affiliated Institutions

Related Publications

Brca2 (XRCC11) Deficiency Results in Radioresistant DNA Synthesis and a Higher Frequency of Spontaneous Deletions

<i>BRCA1</i> and <i>BRCA2</i> mutations account for a large proportion of ovarian carcinoma cases

Adjuvant Olaparib for Patients with <i>BRCA1</i> - or <i>BRCA2</i> -Mutated Breast Cancer

Promoter Hypermethylation and BRCA1 Inactivation in Sporadic Breast and Ovarian Tumors

The Breast Cancer Susceptibility Gene BRCA1 Is Required for Subnuclear Assembly of Rad51 and Survival following Treatment with the DNA Cross-linking Agent Cisplatin

Publication Info

External Links

Social Impact

Citation Metrics

Cite This

Identifiers

Data Quality