Many attempts have been made to analyse short DNA fragments from the blood that are associated with cancer. The critical limitation is that these cancer-associated DNA fragments are very low in concentration, and are hidden amongst a sea of other ‘background’ DNA within the blood. This project takes a game-changing approach by analysing longer DNA fragments and comparing the patterns with thousands of known brain tumours to accurately identify the type of brain tumour. This project will also investigate the DNA content across several blood components such as platelets and white blood cells. This approach has never been tested in childhood brain cancer patients.

This blood test technology aims to help children with brain cancer by providing a non-invasive diagnostic that: (1) identifies those children showing neurological symptoms who need brain scans; (2) assist surgeons in surgical planning; (3) identifies those children who may be able to avoid surgery, since some tumours do not benefit from surgery. In addition, this blood test may potentially show whether a tumour is responding to treatment, and whether it is growing back or not.

Methylation profiling of circulating DNA in paediatric brain tumour patients

Most children with brain tumours first come to medical attention with headaches and other neurological symptoms. Because imaging is expensive, a child is often just treated for their symptoms, hoping they get better, without actually being diagnosed. But sometimes, the disease ends up being a brain tumour. Treating these tumours can be difficult, since the developing brain is very sensitive to neurosurgery, radiation, and chemotherapy. We need an earlier, cheaper, and easier test to reliably diagnose and subclassify paediatric brain tumours. This would not only help identify children who do need brain scans, it would also help neurosurgeons if they knew exactly what kind of tumour they were dealing with while planning surgery. This might even help some children avoid surgery altogether, since some tumours don’t benefit from surgery, or if the blood test says it’s unlikely to even be a tumour. It would also be helpful if that same test could tell whether a tumour is responding to treatment, and whether it is growing back or not.

The Nervous System Tumour Bank at Northwestern University in Chicago recently collaborated with scientists from Toronto to show that a new blood test, called “cell-free methylated DNA immunoprecipitation and high-throughput sequencing” (cfMeDIP-seq), could accurately diagnose the presence and type of brain tumour in adult patients. This technique detects fragments of tumour DNA in the circulating blood, and tests it to see if it matches any pattern of DNA in a large reference library consisting of thousands of brain tumours. While cfMeDIP-seq is already being developed for use in adults with brain tumours, it has not yet been explored in children. Northwestern Medicine, in partnership with Lurie Children’s Hospital of Chicago, has the required technical expertise and paediatric brain tumour patient volume to advance cfMeDIP-seq for the care of children with CNS tumours.