Funded by The Little Princess Trust and administered by CCLG
Lead investigator: Dr Sarra Ryan, Newcastle University
Award: £196,110.00
Awarded March 2022
The first DNA sequence of a normal human genome (called a reference genome) was released in 2003, which was a huge advance for medical research. Scientists could compare samples of cancer to this reference genome for the first time, which helped to find thousands of problems in patient’s DNA that can cause cancer (called genetic variants). These studies have massively improved the survival and long-term health of cancer patients by helping to find drugs that target the specific errors in their DNA, and by helping doctors know the severity of the cancer straight away so they can choose the best treatment.
However, around 10% of the human genome was not recorded in the first reference genome. This 10% used to be called ‘junk DNA’ because they did not know what it did or if it had any use at all. We now know that the ‘junk DNA’ includes parts of the genome called the ‘centromere’ and ‘telomere’, which are essential for cell division. Problems with centromeres and telomeres can lead to changes to a cell’s genome and to cancer development, but we don’t know what effect genetic variants in them have because the lack of a full reference genome.
In May 2021, a new human reference genome was released which included centromeres and telomeres. Ground-breaking technologies were used to produce it that we can’t use them on patient samples, as it is very expensive and needs a lot of human cells.
The research team Newcastle University, led by Dr Sarra Ryan, plan to overcome these issues by developing a new way to measure the amount of genetic variation within the centromere. In a small study, they have already shown that there are unusually high levels of genetic variation within the centromere. This could be important in childhood cancer development, but more data are needed. This project will study more than 2000 patients’ DNA, which Dr Sarra Ryan hopes will enable the impacts of genetic variants within the centromere to be explored for the first time, potentially improving the treatment and survival of childhood cancer patients.