Detection of mutation profiles and tumor mutation burden of cerebrospinal fluid circulating DNA by a cancer genomic panel sequencing in glioma patients

Abstract

Background and aims: Circulating tumor DNA (ctDNA) has been recognized as a reliable source to reflect the molecular and genetic landscape of corresponding tumors in recent years. In this study, we tested the application of a cancer genomic panel sequencing on the cerebrospinal fluid (CSF)-derived ctDNA for the less invasive detection and diagnosis of glioma.

Materials and methods: CtDNA was extracted from 26 CSF samples and subject to a cancer genomic panel sequencing of 520 genes to analyze the mutation profiles and tumor mutation burden (TMB), which were compared with their corresponding tumor DNA samples. Associations between mutations or TMB and clinical characteristics were also evaluated.

Results: A high detection rate of ctDNA (24/26, 92.3%) was observed in CSF. CtDNA mutations had high concordance rates with tumor DNA, especially in non-copy number variations and in glioblastoma. CSF ctDNA TMB also exhibited a strong correlation with tumor DNA TMB (R² = 0.879, P < 0.001), particularly in glioblastoma (R² = 0.992, P < 0.001). Age was significantly associated with CSF ctDNA TMB in glioma patients.

Conclusion: We established a less invasive but effective molecular diagnostic approach using a cancer genomic panel sequencing system targeting CSF ctDNA for glioma, especially in glioblastoma.

Keywords: Cerebrospinal fluid; Circulating tumor DNA; Copy number variation; Glioma; Tumor mutation burden.