Detection of cell‐free DNA fragmentation and copy number alterations in cerebrospinal fluid from glioma patients

Glioma is difficult to detect or characterize using current liquid biopsy approaches. Detection of cell‐free tumor DNA (cftDNA) in cerebrospinal fluid (CSF) has been proposed as an alternative to detection in plasma. We used shallow whole‐genome sequencing (sWGS, at a coverage of 50% of fragments below 150 bp. CSF cell‐free DNA fragment length distributions showed 10‐bp periodic peaks, which were decreased in samples where SCNAs were detected. SCNAs and DNA fragmentation patterns in sWGS data can enhance tumour detection using CSF samples. Graphical Abstract Gliomas are challenging to detect based on cell‐free tumor DNA (cftDNA) in body fluids. In this study, a combined analysis of somatic copy number alterations (SCNA) and DNA fragmentation patterns based on shallow whole genome sequencing (sWGS) improves cftDNA detection in cerebrospinal fluid (CSF).