Distinct DNA methylation profiles in ovarian serous neoplasms and their implications in ovarian carcinogenesis

OBJECTIVE: The purpose of this study was to analyze DNA methylation profiles among different types of ovarian serous neoplasm, which is a task that has not been performed. STUDY DESIGN: The Illumina beads array (Illumina Inc, San Diego, CA) was used to profile DNA methylation in enriched tumor cells that had been isolated from 75 benign and malignant serous tumor tissues and 6 tumor-associated stromal cell cultures. RESULTS: We found significantly fewer hypermethylated genes in ighgrade serous carcinomas than in low-grade serous carcinoma and borderline tumors, which in turn had fewer hypermethylated genes than serous cystadenoma. Unsupervised analysis identified that serous cystadenoma, serous borderline tumor, and low-grade serous carcinomas tightly clustered together and were clearly different from high-grade serous carcinomas. We also performed supervised analysis to identify differentially methylated genes that may contribute to group separation. CONCLUSION: The findings support the view that low-grade and highgrade serous carcinomas are distinctly different with low-grade, but not high-grade, serous carcinomas that are related to serous borderline tumor and cystadenoma.