De novo DNA methylation and acquired cisplatin resistance in an ovarian cancer cell model. A) Cisplatin-sensitive A2780 epithelial ovarian cancer cells were treated with 70% of GI50 dose of cisplatin. Surviving cells (Round1 A2780) were expanded and treated with the subsequent 70% GI50 dose (total of five rounds of drug treatment). The GI50 values for both parental and cisplatin-treated A2780 sublines were measured by MTT assay. B) DMH microarrays were performed on Round1, Round3 and Round5 A2780 cells, and the number of hypermethylated genes for each round was determined using various fold-change cutoffs (1.5-fold or 1.7-fold) and plotted as a function of cisplatin GI50. The correlations were determined by Spearman correlation. C) mRNA expressions in parental (cisplatin-sensitive) and Round5 (cisplatin-resistant) A2780 cells were measured by Human U133 plus 2.0 GeneChips (Affymetrix, Santa Clara, CA). Two-dimensional hierarchical clustering of the 3127 significantly up- or down-regulated probes done by Cluster  revealed distinctively different mRNA expression profiles of the two A2780 sublines (detailed plot provided in Additional file 2).