Exploiting transcription of repetitive DNA to study early events in colorectal cancer

Despite many advances, cancer remains a leading cause of death worldwide, partly due to limited knowledge of the changes that occur in the early stages of disease. Research into early changes has focused mainly on unique DNA, such as protein coding sequences, and has overlooked 55% of our DNA which is made up of repetitive sequences, such as LINE-1s, that are inactive in normal cells but active in cancer. 

Although it is difficult to distinguish and study individual elements, we have identified a LINE-1 whose activation is linked to the silencing of a tumour suppressor gene and whose product can be detected in the blood of people with colon cancer, highlighting LINE-1s’ potential as therapeutic targets and as tools for screening. I will build on this knowledge to investigate: why and which LINE-1s become active in colorectal cancer and the effects of their activation.

My research will determine the potential of using LINE-1s products as tests for early detection of colorectal cancer.