title: High-throughput DNA hypermethylation profiling in different ovarian epithelial cancer subtypes using universal bead array.
abstract: DNA hypermethylation is common and plays a critical role in the regulation of gene expression. It is considered a major cause of carcinogenesis. High-throughput profiling method has been developed to analyze the methylation status of hundreds of pre-selected genes simultaneously. The aim of this study was to analyze promoter hypermethylation profiles of each subtype of ovarian epithelial cancer (OEC), to improve the understanding of the role of epigenetic silencing in carcinogenesis. DNA hypermethylation profiles on fresh frozen tissue samples of 5 serous, 3 mucinous, 5 endometrioid and 4 clear cell types of OEC, as well as 5 normal ovarian tissue samples as control. We used a high-throughput method for analyzing the hypermethylation status of 1,505 CpG loci selected from 871 genes simultaneously by GoldenGate Methylation Cancer Panel I (Illumina Human-6 v2 Expression BeadChip). Methylation status of seven genes was verified by methylation specific PCR (MSP). We identified 20, 37, 15 and 56 hypermethylated CpG locations in serous, mucinous, endometrioid and clear cell type OEC compared to control. Only 6 CpG loci were commonly hypermethylated across all subtypes of OEC. Hypermethylated loci of serous 17 (81.0%) and endometrioid type 10 (71.4%) were identical to that of clear cell type. However, mucinous type showed 17 peculiar loci (43.6%) out of 39 hypermethylated loci. The unique DNA hypermethylation patterns identified in different OEC subtypes suggest that their cause may involve different epigenetic mechanisms and the Bead chip used in this study is a useful tool to analyze DNA hypermethylation.
authors.affiliation: Department of Obstetrics and Gynecology, Medical Research Institute, School of Medicine, Pusan National University, Gyeongsangnam-do 626-770, Republic of Korea.
authors.forename: Man Soo
authors.initials: MS
authors.lastname: Yoon
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Suh
authors.forename: Kyung Un
authors.initials: KU
authors.lastname: Choi
authors.forename: Mee Young
authors.initials: MY
authors.lastname: Sol
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Shin
authors.forename: Won Young
authors.initials: WY
authors.lastname: Park
authors.forename: Jung Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Seong Muk
authors.initials: SM
authors.lastname: Jeong
authors.forename: Woo Gyeong
authors.initials: WG
authors.lastname: Kim
authors.forename: Na Ri
authors.initials: NR
authors.lastname: Shin
mesh_terms: D000328:Adult; D000368:Aged; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods*