Cerebrospinal fluid circulating tumour DNA as a liquid biopsy for central nervous system malignancies

The molecular characterization of central nervous system (CNS) malignancies is crucial for obtaining the correct diagnosis and prognosis, and to guide the optimal therapeutic approach. However, obtaining surgical specimens can be challenging because of the anatomical location of the tumour and may limit the correct characterization of these malignancies. Recently, it has been shown that the cerebrospinal fluid (CSF) circulating tumour DNA (ctDNA) can be used as a liquid biopsy to characterize and monitor CNS malignancies and here we review its implications and advances.

In the last 5 years, several groups including ours have shown that ctDNA is highly present in the CSF, in larger amounts than in plasma, and that ctDNA can be sequenced to provide information about the diagnosis and prognosis of brain malignancies. Furthermore, the analysis of CSF ctDNA has allowed the selection of optimal therapeutic approaches monitoring response to treatment and tracking tumour evolution, providing crucial information about the molecular changes during tumour progression.

Here, we review the recent discoveries and data relative to CSF ctDNA and discuss how CSF ctDNA can be used as a liquid biopsy to facilitate and complement the clinical management of patients with CNS malignancies.