OBJECTIVE: To study how to identify patients with "triple negative" sporadic breast cancers (BCs) having BRCA1 silenced or down-regulated due to epigenetic BRCA1 inactivation. STUDY DESIGN: We selected, from our database, patients diagnosed with BC between 1995 and 2001 with tumors exhibiting the "triple negative" phenotype. "Triple positive" tumors were used as controls. BRCA1 protein expression was determined by immunohistochemistry. Methylation specific polymerase chain reaction (PCR) and bisulfite sequencing on genomic DNA were used to assess BRCA1 promoter methylation. BRCA1 m-RNA expression analysis was conducted by real-time PCR. RESULTS: Forty-four triple negative and 68 controls (triple positive) were eligible for our analysis. BRCA1 promoter methylation was present in 31.8% of triple negative and in 20.6% of triple positive cases. BRCA1 was inactivated (absent BRCA1 m-RNA expression and lack of BRCA1 protein) in 21.4% of tumors with BRCA1 promoter methylation, as compared with 6% of non-methylated ones (p=0.0453). CONCLUSION: BRCA1 inactivation due to promoter methylation could play an important role in some sporadic BC cases. Patients with this signature could represent the basis for prospective studies aiming to compare clinical response to different drugs.
BRCA1 expression in triple negative sporadic breast cancers / E. Galizia, G. Giorgetti, G. Piccinini, A. Santinelli, C. Loretelli, F. Bianchi, D. Gagliardini, G. Carbonari, E. Pisa, L. Belvederesi, R. Bracci, C. Ferretti, F. Corradini, R. Cellerino. - In: ANALYTICAL AND QUANTITATIVE CYTOLOGY AND HISTOLOGY. - ISSN 0884-6812. - 32:1(2010 Feb), pp. 24-29.
|Titolo:||BRCA1 expression in triple negative sporadic breast cancers|
|Parole Chiave:||BRCA1; breast cancer; somatic inactivation|
|Settore Scientifico Disciplinare:||Settore MED/06 - Oncologia Medica|
Settore MED/04 - Patologia Generale
Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica
Settore BIO/13 - Biologia Applicata
Settore MED/03 - Genetica Medica
|Data di pubblicazione:||feb-2010|
|Appare nelle tipologie:||01 - Articolo su periodico|
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