Graph.1;

The diagram shows a representative region of genomic DNA in a normal cell. The region shown contains repeat-rich, hypermethylated pericentromeric heterochromatin and an actively transcribed tumor suppressor gene (TSG) associated with a hypomethylated CpG Island (indicated in red). In tumor cells, repeat-rich heterochromatin becomes hypomethylated and this contributes to genomic instability, a hallmark of tumor cells, through increased mitotic recombination events. De novo methylation of CpG Islands also occurs in cancer cells and can result in the transcriptional silencing of growth-regulatory genes. These changes in methylation are early events in tumorigenesis.