Tumours can form without any mutation in the base sequence, because abnormal methylation can wrongly switch genes on or off. It contributes to tumour formation in two ways.1. Hypermethylation of tumour suppressor genes
Increased methylation of the promoter of a tumour suppressor gene stops transcription factors binding and condenses the chromatin. The gene is not transcribed, so the protein that slows cell division is not made. Cells divide uncontrollably and a tumour forms. Hypermethylation of tumour suppressor genes, such as BRCA1, is found in many cancers, including some breast cancers.2. Hypomethylation of oncogenes
Decreased methylation of a proto-oncogene increases its transcription. The gene acts as an oncogene: its protein is over-produced and cell division is permanently stimulated.Tumour cells often show both: hypermethylation at specific promoters, and hypomethylation across much of the rest of the genome.Worked example: in one set of data, the promoter of a tumour suppressor gene was 8% methylated in normal breast tissue and 64% methylated in tumour tissue.64 ÷ 8 = 8 times greater in the tumour This increased methylation would reduce transcription of the gene, which supports the idea that silencing it contributed to the tumour. However, a correlation does not prove causation: the methylation could be a result of the cancer rather than its cause.Because methylation is reversible, drugs that stop methyl groups being added to DNA can reactivate silenced tumour suppressor genes.
Increased methylation of the promoter of a tumour suppressor gene stops transcription factors binding and condenses the chromatin. The gene is not transcribed, so the protein that slows cell division is not made. Cells divide uncontrollably and a tumour forms. Hypermethylation of tumour suppressor genes, such as BRCA1, is found in many cancers, including some breast cancers.2. Hypomethylation of oncogenes
Decreased methylation of a proto-oncogene increases its transcription. The gene acts as an oncogene: its protein is over-produced and cell division is permanently stimulated.Tumour cells often show both: hypermethylation at specific promoters, and hypomethylation across much of the rest of the genome.Worked example: in one set of data, the promoter of a tumour suppressor gene was 8% methylated in normal breast tissue and 64% methylated in tumour tissue.