Publications

Abstract

DNA methylation is an epigenetic mark that shows considerable promise in early cancer diagnostics, including as a marker of Epithelial Ovarian Cancer (EOC). However, few studies to date have studied global changes in DNA methylation in EOC. To identify epigenetic-based biomarkers for diagnosis of ovarian cancer, we developed a genome-wide integrative strategy to find genes commonly inactivated in clinical samples and methylated in high grade serous EOC. DNA methylation profiling using MeDIP-Chip confirmed that the majority of the genes re-expressed in EOC cell lines A2780 and CaOV3 by 5-Aza-2-deoxycitidine (5-Aza-dC) exhibited CpG island promoter DNA methylation and 15/21 candidate genes exhibited hypermethylation in multiple EOC cell lines. Using methylation-specific headloop PCR analysis we identified a panel of six gene promoters (ARMCX1, ICAM4, LOC134466, PEG3, PYCARD & SGNE1) where hypermethylation discriminated 28 serous EOC versus 14 normal ovarian surface epithelial cells (OSE) (ROC of 0.98). Notably, CpG sites across the transcription start site of a potential long-intergenic non-coding RNA (lincRNA) gene (LOC134466), were hypermethylated in 81% of serous EOC and could differentiate tumours from OSE (p <0.05). We propose that this novel biomarker panel holds great potential for an early stage diagnostic test for high grade serous ovarian cancer.