title: Contribution of epigenetic alteration of BRCA1 and BRCA2 genes in breast carcinomas in Tunisian patients.
abstract: OBJECTIVE
  The aim of this study was to evaluate the contribution of the BRCA1 and BRCA2 promoter methylation in the pathogenesis of sporadic breast cancer in Tunisian patients.
  
  
  METHODS
  Breast carcinoma tissues (n=117) and available paired normal breast tissues (n=65) from Tunisian women who had no family history were investigated for the methylation status of BRCA1 and BRCA2 promoters using methylation-specific PCR. Breast specimens from women without carcinoma (16 fibroadenomas and 5 mastopathies) were used as control.
  
  
  RESULTS
  Hypermethylation of BRCA1 and BRCA2 promoters was detected respectively in 60.7% and 69.2% of the carcinoma tissues, and in only 7.7% and 4.6% of the paired normal breast tissues. None of the fibroadenomas and mastopathies showed hypermethylation. Correlations were found between BRCA1 and BRCA2 hypermethylation and decrease in their mRNA expression (p=0.02 and p=0.009, respectively). Moreover, BRCA1 methylation correlates with patients age (p=0.01) and triple negative (ER-, PR-, HER2-) tumors (p=0.01). Patients with methylated BRCA1 and/or BRCA2 had a significant prolonged survivals compared to those with unmethylated tumors (p=0.002).
  
  
  CONCLUSIONS
  Our results suggest an important role of BRCA1 and BRCA2 promoter methylation in breast cancer development in the Tunisian population.
authors: Department of Pathology, Farhat Hached Hospital, Sousse, Tunisia.
authors: R
authors: R
authors: Ben Gacem
authors: M
authors: M
authors: Hachana
authors: S
authors: S
authors: Ziadi
authors: K
authors: K
authors: Amara
authors: F
authors: F
authors: Ksia
authors: M
authors: M
authors: Mokni
authors: M
authors: M
authors: Trimeche
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014416:Tunisia