Bivalent chromatin domains in ovarian tumours at initial presentation identify genes predisposed to DNA hypermethylation during acquired resistance to chemotherapy [gene expression]

We have used ChIP-seq to characterize genome-wide positioning of H3K4me3 and H3K27me3 associated chromatin in primary high-grade serous ovarian carcinoma and normal ovarian surface and fallopian tube tissue. Sets of genes with proximal bivalent marks were defined using this data and subsequently evaluated as signatures of systematic change in DNA methylation and gene expression between pairs of tissue samples taken from patients at primary presentation and relapse following chemotherapy. Gene expression microarrays from primary tumours were used to assess transcriptional associations of chromatin marks identified in tumours through ChIP-seq RNA was extracted from four primary tumours and hybridized to Affymetrix microarrays. For each tumour, distribution of mas5 detection calls was compared for gene sets with H3K4me3 or H3K27me3 marks.