CpG island hypermethylation

[1] Hypermethylation is linked to methyl-binding proteins, DNA methyltransferases and histone deacetylase, but the degree to which this process selectively silences tumor suppressor genes remains a research area.

[3] Cancer epigenetic silencing in its current state was born in the labs of Baylin and Jones,[3] where it was proven that CpG island hypermethylation was a common inactivation mechanism of the tumor suppressor gene p16INK4a.

The introduction of methylation-specific PCR and sodium bisulfite modification added tools to the belt of cancer epigenetics research,[3][4] and the list of candidate genes with aberrant methylation of their CpG islands has been growing since.

[5] Initially, the presence of alterations in the profile of DNA methylation in cancer was seen as a global hypomethylation of the genome that would lead to massive overexpression of oncogenes with a normally hypermethylated CpG island.

[1] The association of transcriptional silencing of tumor suppressor genes with hypermethylation is the foundation upon which this subset of cancer epigenetics stands.

It is evident that the hypomethylation of the CpG island in normal cells provides no additional steric hindrance to future binding.

The majority of CpG pairs in mammals are chemically modified by the covalent attachment of a methyl group to the C5 position of the cytosine ring.

Colorectal cancer will not necessarily have the same set of hypermethylated CpG islands as in a glioma, and this clinical distinctness of tumors can be interpreted by doctors.

CpG island hypermethylation shows promise for molecular monitoring of patients with cancer, and is also a potential target for therapeutic use.

An algorithm to find functional DNA methylation in cancer cells
Methylation of cytosine to 5- methylcytosine: DNA methylation is the addition of a methyl group to the DNA that happens at cytosine . The image shows a cytosine single ring base and a methyl group added on to the 5 carbon. In mammals, DNA methylation occurs almost exclusively at cytosine chains that are followed by guanine .
In a normal cell, the CpG island is hypomethylated, as can be seen from the unfilled stubs, but the genome , in general, is methylated, as can be seen from the filled in stubs. In contrast, in the cancer cell, the CpG island is more likely to be methylated, and the rest of the genome is hypomethylated. There is a swap of where DNA methylation is found between a normal cell and a cancer cell.
Epigenetic alterations in tumor progression: Epigenetic mistakes are clinically relevant is because they progress over time. The image starts with normal tissue and progresses all the way to metastasis . The global level of methylation decreases as one progresses from normal tissue to metastatic tissue. However, methylation at some CpG islands increases in density. One might be able to use these methylation markers to detect whether a tissue is cancerous or metastatic.