The coming of age of liquid biopsy in neuro-oncology

The clinical role of liquid biopsy in oncology is growing significantly. In gliomas and other brain tumors, targeted sequencing of cell-free DNA (cfDNA) from cerebrospinal fluid (CSF) may help differential diagnosis when surgery is not recommended and be more representative of tumor heterogeneity than surgical specimens, unveiling targetable genetic alterations. Given the invasive nature of lumbar puncture to obtain CSF, the quantitative analysis of cfDNA in plasma is a lively option for patient follow-up. Confounding factors may be represented by cfDNA variations due to concomitant pathologies (inflammatory diseases, seizures) or clonal hematopoiesis. Pilot studies suggest that methylome analysis of cfDNA from plasma and temporary opening of the blood-brain barrier by ultrasounds have the potential to overcome some of these limitations. Together with this, an increased understanding of mechanisms modulating the shedding of cfDNA by the tumor may help to decrypt the meaning of cfDNA kinetics in blood or CSF.