Introduction

Epigenetic modifications cause heritable changes in the expression of the genome without changes in the primary DNA sequence. Epigenetics play an important role in normal development, and epigenetic aberrations have been implicated in a number of human diseases, including cancer. In mammalian cells, two primary mechanisms mold the epigenetic landscape – DNA methylation and histone modifications. The focus of this chapter is to summarize the role of DNA methylation in cancer development and progression.

The importance of DNA methylation

In eukaryotes, DNA methylation is most often found on the 5ʹ position of cytosine bases that are part of CpG dinucleotides (m5C). All types of DNA sequences, including genes, intergenic DNA, and repetitive sequences, are targets of methylation. In normal cells, there is generally a paucity of methylation in regions called CpG islands (CGIs), which are stretches of sequence enriched in CpG dinucleotides. These are often preferentially located in the 5ʹ regions of genes. CpG dinucleotides have been progressively depleted from the eukaryotic genome over the course of evolution, and constitute about 1–2% of mammalian sequences (1). About 70% of the remaining CpG dinucleotides in the mammalian genome are methylated (2). This methylation is thought to play an important role in the co-ordination of chromosomal structure and integrity, and facilitating the functional segregation of active and silent chromatin. Repetitive sequences such as Alu repeats and transposons are frequently heavily methylated, and this state may serve to maintain a transcriptionally repressed state in these regions (3,4).