Cancer is the second leading cause of death globally, and is responsible for an estimated 9.6 million deaths in 2018. Globally, about 1 in 6 death is due to cancer.
Altered patterns of DNA methylation are frequently observed in many human diseases, including most cancers and cardiovascular disease. These changes include both a general loss of methylation from the genome (global hypomethylation), which has been suggested to induce genomic instability and gene-specific CpG island hypermethylation that often induces transcriptional silencing of associated genes. Aberrant DNA methylation changes also occur progressively with age in many apparently healthy tissues in the human body, where it has been proposed to contribute to disease vulnerability1.
In normal cells, DNA methylation occurs predominantly in repetitive genomic regions, including satellite DNA and parasitic elements (such as long interspersed elemnets).
Hypomethylation in tumour cells is primarily due to the loss of methylation from repetitive regions of the genome, and the resulting genomic instability is a hallmark of tumour cells2. Rearrangements that involve the large block of pericentromeric heterochromatin on chromosome 1, for example, are among the most frequent genomic instabilities in many tumour types also contribute to aberrant gene regulation in cancer by TRANSCRIPTIONAL INTERFERENCE or the generation of antisense transcripts. Loss of genomic methylation is a frequent and early event in cancer, and correlates with disease severity and metastatic potential in many tumour types3.