Epigenomic variation in normal and cancer cells

Tumour suppressor genes (TSGs) are DNA blueprints for proteins that stop cells from dividing and increasing in numbers. Each TSG comes in pairs called alleles: one from the mother and one from the father. Cancer is caused by the uncontrolled division of cells; in order for cancers to grow, both tumour suppressor alleles need to be turned off. It was previously thought that the only way to turn off genes like TSGs was through permanent changes to the normal DNA sequence, called mutations. However, another way to turn off genes is to add small chemical “tags” – called methyl groups – to a gene. This causes the DNA blueprints to fold up and become unreadable. Another complexity is that some regions of DNA that are normally folded up because of methylation become de-methylated as cancer progresses. This turns on cancer-promoting genes and increases DNA instability. Therefore, it is important to determine the DNA methylation patterns of all DNA in cancer cells in order to know what and how genes are turned on and off. Jonathan Davies previously received a Junior Graduate Studentship from MSFHR. Now funded with at Senior Graduate Studentship, he is researching techniques to identify genes and regions in normal and cancer genomes that may be turned on or off by DNA methylation. These techniques could be used to tailor treatments to individual patients, leading to improved recovery rates, and avoiding costly and ineffectual treatments.