BRCA1 dysfunction in sporadic basal-like breast cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2007-03

AUTHORS

N C Turner, J S Reis-Filho, A M Russell, R J Springall, K Ryder, D Steele, K Savage, C E Gillett, F C Schmitt, A Ashworth, A N Tutt

ABSTRACT

Basal-like breast cancers form a distinct subtype of breast cancer characterized by the expression of markers expressed in normal basal/myoepithelial cells. Breast cancers arising in carriers of germline BRCA1 mutations are predominately of basal-like type, suggesting that BRCA1 dysfunction may play a role in the pathogenesis of sporadic basal-like cancers. We analysed 37 sporadic breast cancers expressing the basal marker cytokeratin 5/6, and age- and grade-matched controls, for downregulation of BRCA1. Although BRCA1 promoter methylation was no more common in basal-like cancers (basal 14% vs controls 11%, P=0.72), BRCA1 messenger RNA expression was twofold lower in basal-like breast cancers compared to matched controls (P=0.008). ID4, a negative regulator of BRCA1, was expressed at 9.1-fold higher levels in basal-like breast cancer (P<0.0001), suggesting a potential mechanism of BRCA1 downregulation. BRCA1 downregulation correlated with the presence of multiple basal markers, revealing heterogeneity in the basal-like phenotype. Finally, we found that 63% of metaplastic breast cancers, a rare type of basal-like cancers, had BRCA1 methylation, in comparison to 12% of controls (P<0.0001). The high prevalence of BRCA1 dysfunction identified in this study could be exploited in the development of novel approaches to targeted treatment of basal-like breast cancer. More... »

PAGES

2126

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.onc.1210014

DOI

http://dx.doi.org/10.1038/sj.onc.1210014

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1039037705

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/17016441


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