Cerebrospinal Fluid-Derived Genomic Alterations Tracking Glioma

Area of Science:

• Neuro-oncology
• Genomics
• Molecular Diagnostics

Background:

• Diffuse gliomas are aggressive brain tumors characterized by significant heterogeneity and frequent oncogenic mutations.
• Current monitoring and therapeutic guidance often rely on invasive procedures or less sensitive methods.

Purpose of the Study:

• To evaluate the utility of circulating tumor DNA (ctDNA) in cerebrospinal fluid (CSF) as a less invasive tool for monitoring diffuse gliomas.
• To compare the genomic alterations detected in CSF ctDNA with matched tumor tissue and blood samples.

Main Methods:

• Targeted sequencing of ctDNA from CSF, blood, and tumor tissue samples.
• Analysis of somatic alterations and DNA fragmentations in CSF ctDNA.
• Comparison of genetic profiles between CSF ctDNA and tumor tissue DNA.

Main Results:

• CSF ctDNA revealed a broad spectrum of glioma-associated mutations, closely reflecting the genomic profiles of corresponding tumor samples.
• Tumor-specific mutations were detected in 91.67% of both tissue and serial CSF ctDNA samples.
• CSF sequencing demonstrated a comparable or even higher mutation detection rate than tissue sequencing in some patients, with similar average mutation frequencies.

Conclusions:

• CSF ctDNA is a reliable and less invasive candidate for detecting glioma-specific alterations for molecular profiling.
• CSF ctDNA analysis complements existing histopathological, molecular, and imaging diagnostics.
• The findings support the adoption of CSF ctDNA analysis into clinical practice for diffuse glioma management.