Uncovering Brain Tumor Biomarkers in Blood and CSF
Three breakthrough studies may improve diagnosis and monitoring of brain tumors
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.
- L Escudero et al., Nat Commun, 27, 5376 (2020). PMID: 33110059.
- AK Bruzek et al., Clin Cancer Res, [Online ahead of print] (2020). PMID: 33087334.
- University of Michigan (2020). Available at: bit.ly/3krDLQG.
- K Muralidharan et al., Clin Cancer Res, [Online ahead of print] (2020). PMID: 33051308.
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