Minimal invasive detection of circulating biomarkers in pediatric brain tumor patients using liquid biopsy

Brain tumors (BT) are the most common solid tumors in pediatric patients. Invasive diagnostics pose a risk and timely detection of progression remains a major challenge. Liquid biopsies (LBs) are minimally invasive. In BTs plasma LBs are limited by the blood-brain-barrier and in cerebrospinal fluid (CSF) by low volumes. Application of improved LB methodology shows feasibility of tumor classification and early detection. Cell-free DNA (cfDNA) was isolated from CSF and plasma samples and subjected to low-coverage whole-genome-sequencing (lcWGS). Methylation status of cfDNA from CSF was assessed by EPIC array and WGS. Bioinformatic algorithms were adapted to LB specifics. LcWGS recapitulate tumor-specific copy number variants (CNVs) in CSF and plasma samples. Tumor fraction and detection rate of CNVs were significantly higher in CSF compared to plasma samples. CfDNA methylation analysis allowed for tumor classification from CSF. Clinical applicability of LB diagnostics was showcased in a patient (score 0.99) who was not amenable to a surgical biopsy. Non-invasive LBs from CSF and plasma may contribute to earlier tumor detection and timely therapy adjustments in pediatric BT patients.