Specific mechanisms behind cancer gene activation discovered

Genetic changes that turn on cancer genes have been discovered, which may lead to the development of improved methods for predicting and treating cancer.

Researchers from the Salk Institute, California, have shown that the activity of cancer-causing genetic mutations is dependent on the spatial distance between a particular gene and the sequences that regulate the gene. Publishing their findings in Nature, they go on to explain that the activity of the genetic mutations is also reliant on how active the regulatory sequences are.

'If we can better understand why a person has cancer, and what particular genetic mutations are driving it, we can better assess risk and pursue new treatments,' said Dr Jesse Dixon, assistant professor at the Salk Institute and corresponding author of the paper.

Using CRISPR/Cas9 genome editing, the scientists cut DNA in specific locations and introduced genetic mutations. Most of the genetic variants they created had no impact, however, they found that some impacted the expression of nearby genes – leading to the ability of the cell to become cancerous. Furthermore, the type of regulatory sequence introduced was found to have a huge impact on whether or not the cell became cancerous.

The authors hope that their work will help to predict and determine which genetic mutations found in the genomes of cancer are actually causing the disease.

'A gene is like a light and what regulates it are like the light switches,' Dr Dixon said. 'We are seeing that, because of structural variants in cancer genomes, there are a lot of switches that can potentially turn "on" a particular gene.'

Cancer is caused by abnormal overgrowth of cells, and is the second-leading cause of death in the world. Uncovering the specific mechanisms that cause normal cells to become cancer cells, ie, the activation of oncogenes, will aid in the development of novel cancer treatments and in the estimation of a person's risk of developing cancer.

'Our next move is to test whether there are other factors in the genome that contribute to the activation of oncogenes,' explained Dr Zhichao Xu, a postdoctoral fellow at Salk and co-first author of the paper. 'We are also excited about a new CRISPR genome editing technology we are developing to make this type of genome engineering work much more efficiently.'