Genome-wide methylome profiling of normal breast and breast tumors

To improve our understanding of the effect of differential methylation on gene expression between normal and tumor breast cells, we employed high-throughput sequencing technology to determine and compare CpG methylation of normal breast and four breast tumor genomes at single-base resolution. By comparing the methylation profiles between normal and tumor, we identified large hypomethylated zones in associated with large tissue-specific genes and gene deserts. We identified small hypomethylated regions in the methylomes and termed these sites as unmethylated islands (UMI). The UMI are highly correlated with positive regulatory chromatin marks and exhibit differential methylation mainly at the island shores. Our analysis showed there is a complex relationship between genome-wide promoter differential methylation and gene expression. Four other data sets from this study were also deposited at ArrayExpress under accession numbers E-MTAB-1935, E-MTAB-1952, E-MTAB-1958 and E-MTAB-1961.