Authors: V Shilpa Rahul Bhagat C S Premalata V R Pallavi G Ramesh Lakshmi Krishnamoorthy
Publish Date: 2014/01/03
Volume: 35, Issue: 5, Pages: 4277-4284
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 methylationspecific 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 512 and 57 respectively significantly higher p = 0000 and p = 0001 in comparison to benign tumours and normal ovarian tissue where no methylation was seen Expression of BRCA1 was significantly lower in EOCs p = 0003 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 Followup clinical data will reveal the impact of BRCA1 methylation on survivalThe authors thank Dr Sanjay Navani for helping in construction of tissue microarray We also thank Mr Prashant and Mr Shivshankar for their help in immunohistochemical staining of tissue microarray slides We are grateful to Dr V Shanmugam Research Assistant NIMHANS for helping with the statistical analysis
Keywords: