BRCA1 dysfunction in sporadic basal-like breast cancer

• Tipo: Artigo em Revista Científica Internacional
• Data: 2007

Autores

Turner, NC (Autor) Outra; Reis Filho, JS (Autor) Outra; Russell, AM (Autor) Outra; Springall, RJ (Autor) Outra; Ryder, K (Autor) Outra; Steele, D (Autor) Outra; Savage, K (Autor) Outra; Gillett, CE (Autor) Outra; Fernando Schmitt (Autor) FMUP; Ashworth, A (Autor) Outra; Tutt, AN (Autor) Outra

Revista

Título: Oncogene

Vol. 26

Páginas: 2126-2132

ISSN: 0950-9232

Editora: Springer Nature

Indexação

ISI Web of Knowledge - 440 Citações

Scopus - 480 Citações

Outras Informações

ID Authenticus: P-004-BMT

DOI: 10.1038/sj.onc.1210014

Abstract (EN): Basal-like breast cancers forma 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 7