Model of aberrant DNA methylation patterns and its applications in epithelial ovarian cancer / 中华妇产科杂志

ABSTRACT

Objective To profile methylation alterations of cytosine-phosphate-guanosine islands (CGI)in epithelial ovarian cancer and investigate its applications for finding new candidate tumor markers.Methods Cancer cells were obtained by lager microdissection from 20 tissues of frozen-preserved epithelial ovarian tumors.Primary cultured epithelial cells were isolated from 5 tissues of normal ovaries.Differential methylation hybridization(DMH)based on microarray assay Was conducted using DNA to construct the aberrant DNA methylation pattern of epithelial ovarian cancer.MethyLight was conducted to verify the methylation status of 7 hypomethylated promoter CGI detected by DMH in tumor tissues of 87 patients with epithelial ovarian cancer and 42 patients with benigh ovarian diseases.Results The aberrant DNA methylation pattem of epithelial ovarian cancer were included 182 hypermethylated loci and 64 hypomethylated loci,of which the positive loci located more than 25%arrays were 18 and 31,respectively.The methylation ratio of gene LSM2,EGFLAM and CDKN2A in tissue DNA of patients with epithelial ovarian cancer and benign ovarian diseases Was 11%(10/87)versus 33%(14/42),8%(7/87)versus 21%(9/42),9%(8/87)versus 31%(13/42),respectively,which Was significantly decreased in tissues DNA of ovarian cancer than that from benigh ovarian diseases(P＜0.05).Conclusions The aberrant DNA methylation pattern of epithelial ovarian cancer is important for finding new cancer related genes.The promoter CGI of gene ISM2,EGFIAM and CDKN2A may be Hovel candidate for ovarian cancerspecific hypomethylated tumor markers.