title: BRCA1 promoter hypermethylation and protein expression in ovarian carcinoma--an Indian study.
abstract: Mounting evidences suggest that aberrant methylation of CpG islands is a major pathway leading to the inactivation of tumour suppressor genes and the development of cancer. The aim of the current study was to examine the prevalence of the promoter hypermethylation and protein expression of the BRCA1 gene in epithelial ovarian carcinoma (EOC) to understand the role of epigenetic silencing in ovarian carcinogenesis. We studied the promoter methylation of the BRCA1 gene by methylation-specific PCR in a cohort of 88 patients with EOC, 14 low malignant potential (LMP) tumours and 20 patients with benign tumours of the ovary. The expression of the BRCA1 protein by immunohistochemical analysis was carried out in a subset of 64 EOCs, 10 LMP tumours, 10 benign tumours and 5 normal ovarian tissues. The frequencies of methylation in EOCs and LMP tumours were 51.2 and 57%, respectively, significantly higher (p = 0.000 and p = 0.001) in comparison to benign tumours and normal ovarian tissue where no methylation was seen. Expression of BRCA1 was significantly lower in EOCs (p = 0.003). Lack of protein expression correlated with tumour grade and type. The methylation status correlated well with downregulation of BRCA1 expression. Our results clearly demonstrate that hypermethylation of BRCA1 promoter is a frequent event in ovarian cancer. These data support the hypothesis that BRCA1 promoter methylation plays an important role in the functional inactivation of BRCA1. Follow-up clinical data will reveal the impact of BRCA1 methylation on survival.
authors.affiliation: Department of Biochemistry, Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda Road, Bangalore, 560029, India, shilpachadaga@gmail.com.
authors.forename: V
authors.initials: V
authors.lastname: Shilpa
authors.forename: Rahul
authors.initials: R
authors.lastname: Bhagat
authors.forename: C S
authors.initials: CS
authors.lastname: Premalata
authors.forename: V R
authors.initials: VR
authors.lastname: Pallavi
authors.forename: G
authors.initials: G
authors.lastname: Ramesh
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Krishnamoorthy
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000032:analysis*; D000077216:Carcinoma, Ovarian Epithelial; D015331:Cohort Studies; D019175:DNA Methylation; D005260:Female; D019398:Genes, BRCA1; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D046888:Tissue Array Analysis
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human