Cerebrospinal fluid-derived genomic alterations tracking glioma

Abstract Background Diffuse gliomas, characterized by significant heterogeneity, are aggressive brain tumors that commonly harbor oncogenic mutations. Examining the evolutionary changes of circulating tumor DNA (ctDNA) in cerebrospinal fluid (CSF) provides a valuable approach for monitoring disease progression and informing treatment strategies. Methods To assess the genetic alterations profiling associated with glioma, we conducted targeted sequencing of ctDNA from CSF along with matched blood and tumor tissue, aiming to identify somatic alterations and DNA fragmentations. The ctDNA presents in CSF and genomic DNA obtained from the excised tumor were extracted and subsequently subjected to sequencing analysis. The identified glioma-associated mutations from ctDNA in CSF and genome DNA of the resected tumor were compared. Results The genomic profile of glioma in CSF exhibited a broad spectrum of genetic alterations and closely resembled the genomes of tumor samples. A minimum of one mutation specific to the tumor in 91.67% of cases (22/24) was identified. At least one tumor-specific mutation was detected in 91.67% of CSF ctDNA samples (11/12). The average mutation frequencies were similar in CSF and tumor tissue samples. Conclusion 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.