Vancouver, BC – Scientists at the BC Cancer Agency say they have created a way to detect and identify a type of cancer-causing change in DNA, which may lead to ways to reverse those changes with targeted therapies, described in a paper published this month in Nature Genetics.
Building on an existing technology developed at the agency, researchers have developed a method that allows them to find individual genomic alterations in the DNA of a tumour, and compare it to the DNA of a healthy genome.
Some genes have ‘tags’ at the end of them, which usually help normal cells maintain their function. In cancer cells, however, tags get attached to the wrong gene, which causes the gene to either stop working or continue to thrive as an abnormal cell. By identifying those genes whose tags have been altered by the addition of a molecule called methylation – it may be possible to find a drug to reverse these changes in the gene.
"Some of the altered genes are the gatekeepers of the cell," explains Jonathan Davies, an agency researcher and one of the paper’s authors. "If you turn them off, it’s like cutting the brake wire on your car. You can’t make the cells stop and they keep dividing."
The BC Cancer Agency technology has been placing DNA fragments on to a glass chip that also houses the entire human genome. This way, researchers can see which regions of the tumour genome are altered, and compare them with the normal genome, to determine which of the changes are abnormal.
"In the past, people have focused on gene mutation in DNA, but this is DNA being modified without mutations," says Dr Wan Lam, a senior scientist at the agency. "This is one type of change to DNA that has been invisible to earlier technology."
While the technology is currently being tested in the lab setting, the researchers are using human tissue samples to evaluate its effectiveness. They expect that within three years, it should be ready for the clinical setting.
‘This is important because we can now identify the changes in genes across the whole genome, so we can target those changes that are reversible, plus, we will be able to monitor the efficacy of therapies in patients" says Dr Lam.
Support for this research was provided by the Michael Smith Foundation for Health Research and the Canadian Institutes of Health Research.