Megabase-sized hypomethylation zones in tumor cells. The majority of large hypomethylated zones in the MCF7 genome occur in the genomic region with low gene density. (A) Hypomethylated zones in breast tumor genomes are located in low-gene-density regions in chromosome 1 (lowest line). In MCF-7 and MDA-MB-231 genomes, the hypomethylated zones are in association with these low-gene-density regions, and the P-values of Fisher’s exact test are <0.01. Arrows represent the hypomethylated fragile sites in MCF-7 cell line genome, FRA1A (1p35–36.1), FRA1B (DAB1), FRA1C (1p31.2), FRA1E (DPYD), FRA1G (1q25.1), and FRA1H (USH2A and ESRRG). (B) The 12q24.31–32 hypomethylated regions (white bars) are found in the genomes of MCF-7 (P < 0.01), MDA-MB-231 (P < 0.01), and primary breast tumor (P < 0.01) as compared with normal breast genome. The red horizontal lines represent ratios of one between signals of ExoIII-digested and mock-digested DNA.