Cerebrospinal Fluid-Derived Genomic Alterations Tracking Glioma

Diffuse gliomas are aggressive brain tumors known for heterogeneity and frequent oncogenic mutations. Our study harnessed circulating tumor DNA (ctDNA) in cerebrospinal fluid (CSF) as a less invasive method for disease monitoring and guiding therapeutic interventions. Through targeted sequencing of ctDNA from CSF and matched blood and tumor tissue samples, we aimed to identify glioma-associated somatic alterations and DNA fragmentations. The identified glioma-associated mutations from ctDNA in CSF and genome DNA of the resected tumor were compared, revealed a broad genetic alteration spectrum within CSF ctDNA, closely reflecting the genomic profiles of corresponding tumor samples. And we found 91.67% (11/12) of tissue samples analyzed by next-generation sequencing (NGS), a minimum of one tumor-specific mutation was present. Also, at least one tumor-specific mutation was detected in 91.67% of serial CSF ctDNA samples (11/12). In some patients, CSF sequencing showed higher mutation detection rate compared to tissue sequencing. Moreover, the average mutation frequencies were similar between CSF and tumor tissue samples. These results support that CSF ctDNA is a reliable candidate for detecting glioma-specific alterations for molecular profiling, complements the histopathological, molecular and imaging defect, and can be adopted into clinical practice.