Uncovering Brain Tumor Biomarkers in Blood and CSF

Although diagnosing brain tumors early is critical for better outcomes, accessing biomarkers in the brain presents unique challenges – a lack of minimally invasive methods, a complex location, and the natural blockade created by the blood-brain barrier, to name a few. Medulloblastomas and gliomas are the most common brain tumors in children and adults, respectively. Genomic characterization of medulloblastomas may lead to more precise molecular diagnoses – but biopsies are risky and may not accurately represent the tumor.

Analyzing circulating tumor DNA (ctDNA) in cerebrospinal fluid (CSF) may offer a route to accurate characterization and diagnosis of pediatric brain tumors. In a proof-of-concept study, researchers at the Vall d’Hebron Institute of Oncology showed that CSF ctDNA holds valuable information about a tumor’s mutations and provides valuable information about prognosis and intratumoral genomic heterogeneity (1).

Researchers at the University of Michigan had a similar idea for children with high-grade gliomas. Collecting CSF is not currently part of standard care, so they applied nanopore genetic sequencing technology through a handheld device to investigate actionable alterations in patient CSF samples, which they confirmed with well-established methods (2). “This approach suggests we can rapidly and reliably detect key tumor-driving mutations in high-grade gliomas with very small samples – overcoming some of the barriers that were preventing the use of spinal cord fluid in diagnosing and monitoring these patients,” said principal investigator Carl Koschmann (3).

In a third study, researchers at Massachusetts General Hospital investigated TERT mutations – common promoters of tumor growth not previously detected in circulating free DNA of gliomas. A new digital droplet polymerase chain reaction (ddPCR) blood test compared glioma patients’ blood samples with their tumor biopsy tissue (4). The test accurately detected two TERT gene mutations with a 62.5 percent sensitivity rate – significantly higher than other assays that detect TERT mutations in the blood.