title: Epigenetic inactivation of BRCA1 through promoter hypermethylation in ovarian cancer progression.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai First Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yan-Qiu
authors.initials: YQ
authors.lastname: Wang
authors.forename: Qin
authors.initials: Q
authors.lastname: Yan
authors.forename: Jia-Rong
authors.initials: JR
authors.lastname: Zhang
authors.forename: Shuang-Di
authors.initials: SD
authors.lastname: Li
authors.forename: Yi-Xia
authors.initials: YX
authors.lastname: Yang
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Wan
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D010053:Ovary / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic; D015854:Up-Regulation
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D015415:Biomarkers