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 laser 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 benign ovarian diseases.
Results: The aberrant DNA methylation pattern 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 benign 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 LSM2, EGFLAM and CDKN2A may be novel candidate for ovarian cancer-specific hypomethylated tumor markers.