Ploidy and large-scale genomic instability consistently identify basal-like breast carcinomas with BRCA1/2 inactivation.
Cancer Res
; 72(21): 5454-62, 2012 Nov 01.
Article
en En
| MEDLINE
| ID: mdl-22933060
ABSTRACT
BRCA1 inactivation is a frequent event in basal-like breast carcinomas (BLC). However, BRCA1 can be inactivated by multiple mechanisms and determining its status is not a trivial issue. As an alternate approach, we profiled 65 BLC cases using single-nucleotide polymorphism arrays to define a signature of BRCA1-associated genomic instability. Large-scale state transitions (LST), defined as chromosomal break between adjacent regions of at least 10 Mb, were found to be a robust indicator of BRCA1 status in this setting. Two major ploidy-specific cutoffs in LST distributions were sufficient to distinguish highly rearranged BLCs with 85% of proven BRCA1-inactivated cases from less rearranged BLCs devoid of proven BRCA1-inactivated cases. The genomic signature we defined was validated in a second independent series of 55 primary BLC cases and 17 BLC-derived tumor cell lines. High numbers of LSTs resembling BRCA1-inactivated BLC were observed in 4 primary BLC cases and 2 BLC cell lines that harbored BRCA2 mutations. Overall, the genomic signature we defined predicted BRCA1/2 inactivation in BLCs with 100% sensitivity and 90% specificity (97% accuracy). This assay may ease the challenge of selecting patients for genetic testing or recruitment to clinical trials of novel emerging therapies that target DNA repair deficiencies in cancer.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
2_ODS3
Problema de salud:
2_muertes_prematuras_enfermedades_notrasmisibles
Asunto principal:
Ploidias
/
Neoplasias de la Mama
/
Pruebas Genéticas
/
Carcinoma Ductal de Mama
/
Genes BRCA1
/
Genes BRCA2
/
Inestabilidad Genómica
Tipo de estudio:
Diagnostic_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
Cancer Res
Año:
2012
Tipo del documento:
Article
País de afiliación:
Francia