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 tumours, targeted sequencing of cell-free DNA (cfDNA) from CSF may help differential diagnosis when surgery is not recommended and be more representative of tumour 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 haematopoiesis. Pilot studies suggest that methylome analysis of cfDNA from plasma and temporary opening of the blood-brain barrier by ultrasound have the potential to overcome some of these limitations. Together with this, an increased understanding of mechanisms modulating the shedding of cfDNA by the tumour may help to decrypt the meaning of cfDNA kinetics in blood or CSF. Berzero et al. review the benefits and limitations of using cell-free DNA from plasma or cerebrospinal fluid in the differential diagnosis and follow-up of patients with brain tumours.

Automated summary

The clinical use of liquid biopsy, specifically the analysis of cell-free DNA from plasma or cerebrospinal fluid, is increasingly important in oncology, particularly for brain tumours. It can provide valuable information for differential diagnosis, patient follow-up, and identifying targetable genetic alterations. However, there are challenges such as concomitant pathologies and invasive procedures to obtain cerebrospinal fluid, which could affect the accuracy and interpretation of the results. Further research and understanding of the mechanisms behind cfDNA shedding by tumours are needed to fully exploit its potential in clinical practice.