Abstract P2-09-04: DNA methylation landscapes in ER-negative breast cancer

Abstract

Abstract The biological significance of DNA methylation in the regulation of gene expression and its role in cancer is increasingly recognized. The underlying hypothesis of this study is that strategic global approaches will identify aberrantly methylated genes that underlie the pathogenesis of ER-negative (ER−) breast cancer (BC). We used the Infinium HumanMethylation450 BeadChip to profile the methylome of ER− breast cancers. The 450K array includes 485,577 cytosine positions of the human genome. From these cytosine sites, 99.3% are CpG dinucleotides. Whole genomic DNA from 20 primary ER− and 8 normal breast tissue samples were assayed for genome-wide methylation using the Illumina 450K array. We had 8634 hypermethylated CpGs or 1.8% of the 485,577 sites on the 450K array. The proportion with hypermethylation was higher for promoter regions (2.1% vs 1.5%), and highest for the “FirstExon” promoter subregion. Of the 8634 CpGs, 2980 (adjusted p = 0.05) were differentially methylated between tumor and normal samples. This resulted in 206 genes with significant hypermethylation (all mean breast cancer betas >= −0.2, and ratio of tumor to normal mean beta >= 2.0). Estrogen receptor-negative BC is a more aggressive form than ER positive BC with approximately double the incidence in African Americans than in Caucasian Americans. The emerging differential methylation pattern within hormone receptor negative breast cancers would further help stratify them into distinct subgroups. Promotor methylation being potentially reversible, methylated genes may serve as future molecular targets for demethylating therapies. Support: Komen Foundation: KG110218 Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-09-04.