Epigenetic inactivation of BRCA1 through promoter hypermethylation in ovarian cancer progression


  • The work was carried out at the Shanghai First Hospital, School of Medicine, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China.

Dr Xiao-Ping Wan, Department of Obstetrics and Gynecology, International Peace Maternity and Children Health Care Hospital, Shanghai Jiao Tong University, 910 Hengshan Road, Shanghai 200030, China. Email: wanxp61@126.com


Aim:  The BRCA1 promoter is hypermethylated in ovarian cancer patients. We postulated that this hypermethylation might be involved in ovarian cancer progression.

Methods:  To confirm our hypothesis, tissue and serum samples were collected from ovarian carcinoma patients and categorized according to tumor stage. Healthy or benign ovarian disease tissue samples and corresponding serum samples were used as controls. Breast and ovarian cancer susceptibility gene 1 (BRCA1) promoter methylation levels were detected by real-time polymerase chain reaction (PCR). Real-time PCR was also used to evaluate BRCA1 gene expression, and Western blot was performed to assay the expression of BRCA1 protein.

Results:  BRCA1 showed hypomethylation in 30 normal ovarian and 30 benign ovarian tumors, but showed hypermethylation or methylation in ovarian cancer patients. There was also a significant difference in the BRCA1 promoter methylation levels between different ovarian cancer stages. Compared to stage I and the control groups, there were higher BRCA1 promoter methylation frequencies in stage II and III ovarian cancers. BRCA1 methylation correlated with the loss of BRCA1 expression. BRCA1 promoter in stage I tumors showed hypomethylated.

Conclusion:  Promoter hypermethylation may act as a biomarker for sporadic ovarian cancer progression, but is unlikely to be helpful in the early diagnosis of ovarian cancer.