title: BRCA1promoter hypermethylation in sporadic epithelial ovarian carcinoma: Association with low expression of BRCA1, improved survival and co-expression of DNA methyltransferases.
abstract: The breast cancer susceptibility gene 1 (BRCA1) inactivation in sporadic epithelial ovarian carcinoma (EOC) is common and low BRCA1 expression is associated with promoter hypermethylation. The clinical validation ofBRCA1methylation as a prognostic marker in EOC remains unresolved. The aim of the present study was to determine the aberrant promoter methylation ofBRCA1in benign and malignant ovarian tumor tissues, to establish the association with the clinicopathological significance and the prognostic value. Additionally, the contribution of DNA methyltransferase (DNMT) expression toBRCA1promoter hypermethylation was determined. The rate ofBRCA1methylation was observed to be 35.2% (50/142) in the EOCs; however, no methylation (0/32) was observed in the benign tumors.BRCA1methylation was significantly associated with the downregulation ofBRCA1expression (P<0.001) and the frequency ofBRCA1methylation was greater in the carcinomas of patients whose tumor was bilateral than that of patients with a unilateral carcinoma (P=0.015).BRCA1methylation was significantly associated with the preoperative serum carbohydrate antigen-125 level (P=0.013), improved overall survival (P=0.005) and disease-free survival (P=0.007). In addition, a significant correlation was observed between the co-expression of DNMTs and the methylation status ofBRCA1. Thus, the present study provided support forBRCA1promoter hypermethylation as a prognostic marker for survival in sporadic EOC, and co-expression of DNMTs was observed to contribute toBRCA1promoter hypermethylation.
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Bai
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Obstetrics and Gynecology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xue
authors.affiliation: Department of Obstetrics and Gynecology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Kejun
authors.initials: K
authors.lastname: Guo
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Song
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Zhaojin
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Tianhong
authors.initials: T
authors.lastname: Jia
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Mi
authors.affiliation: Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Enhua
authors.initials: E
authors.lastname: Wang
authors.affiliation: Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Haishan
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Weifan
authors.initials: W
authors.lastname: Yao
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Minjie
authors.initials: M
authors.lastname: Wei
keywords: DNA methyltransferases; breast cancer susceptibility gene 1; immunohistochemistry; methylation; ovarian cancer