Projects we fund

Overview

The human genome – our complete set of DNA – was famously sequenced (decoded) under the Human Genome Project, a massive international collaboration costing around $3 billion, which was declared complete in 2003. Today we have the technology to sequence a person’s genome for around £1,000. We call this Whole Genome Sequencing, or WGS, and it enables us to look for abnormalities (including mutations) within the DNA of an individual. WGS has identified key genes important in the development of childhood cancer. However, although the term ‘whole genome’ is used, 5-10 per cent of the genome remains uncharted. We need to find out how important this part is in disease development. The research team believes that variants or mutations must exist within the DNA sequence that affect the normal function of the centromere. To understand more about leukaemia, we need to find out about the genetic risk factors that contribute to the disease.

What difference will this project make?

This 12-month pilot project will help us better understand the role of the centromere in childhood cancer. This will allow doctors to help children with cancer and children at risk of developing cancer. By developing ways to decode the centromere DNA sequence, we will begin to why children born with the chromosomal abnormality are more likely to develop leukaemia; but also why some with the same abnormality don’t develop it. So the research team will focus on children who have a germline (inherited) chromosomal abnormality with an enormous risk of developing leukaemia. DNA is packaged into chromosomes. Most human cells have 46 chromosomes, arranged into 23 pairs. Each chromosome contains a ‘centromere’ – important in cell division. Centromeres are part of the ‘uncharted’ 5-10 per cent of the genome, which is very difficult to sequence. Research has shown that some people have abnormal centromeres, which increase their susceptibility to cancer. Christine and colleagues recently made a breakthrough discovery that carriers of a rare inherited chromosomal abnormality known as rob(15;21)c, are much more likely to develop leukaemia. They believe that the ‘trigger’ for leukaemia in these children is something in the unique structure of the centromere. Building on this discovery, the research team is developing revolutionary new technologies that will help us decode the complete DNA sequence of the centromere for the first time. Their study will focus on the centromere of the specific rob(15;21)c chromosomal abnormality so we can learn what cause some children to develop leukaemia. This will help us identify children who may be at risk of cancer sooner – and increase their chances of being treated successfully. It will also help us work out how the disease forms, and potentially find ways to stop it.