A feasibility study evaluating the use of circulating tumour DNA in genetic tests, as a proxy for brain cancer biopsy samples


Histological and genetic analysis of a brain biopsy are crucial parts of diagnosing glioma. The process is highly invasive and, additionally, a subset of patients are unsuitable for the procedure. A growing body of evidence is showing plasma circulating DNA, shed from a solid tumour (ctDNA), can be used to look for tumour mutational characteristics (Wan et al., 2017, Komatsubara et al., 2017, Volckmar et al, 2018). Thus diagnosing and monitoring cancer through circulating tumour DNA is increasingly being used as a tool in the Clinical Laboratory (Koessier et al., 2019). For this project, we aim to see if we can apply our conventional glioma laboratory tests to cell-free DNA (cf-DNA) isolated from blood plasma. This would provide diagnostic information for patients where it is not currently available and/or provide options of less invasive testing. Blood plasma ctDNA yield from glioma is low (Bettegowda et al., 2014) and literature as to the utility of glioma ctDNA for conventional genetic testing, has mixed reports of success. Our standard of care tests – 1p19q co-deletion, O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation and Isocitrate Dehydrogenase (IDH) mutation status, cover a range of analytical sensitivities. Thus, by applying our standard laboratory analyses to blood plasma samples, this study could be used to gauge the utility of cell-free DNA in glioma testing.