Next-generation sequencing of circulating tumor DNA in cerebrospinal fluid for detecting gene mutations in central nervous system lymphoma patients.

Background: To evaluate the potential clinical value of cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) in the diagnosis and monitors the central nervous system (CNS) lymphomas.

Methods: This was a prospective study of 17 consecutive patients with B-cell lymphoma: 10 patients with CNS lymphomas and 7 patients with B-cell lymphomas at high clinical risk of CNS relapse. Genomic profiles were performed on the CSF and plasma samples of patients by next-generation sequencing.

Results: In patients with CNS lymphomas, ctDNA was detected in 70.0% of CSF and 60.0% of plasma. The detection rate and gene mutation abundance of CSF were higher than plasma ( = 0.016). CSF had a unique genetic profile. Furthermore, we newly found that gene mutations consistent with plasma or lymphoma-related were also detected in the CSF of the high-risk group without CNS involvement. Analysis of paired plasma and CSF samples from three patients at different time points, changes of CSF ctDNA abundance occurred at the same time or earlier than clinical disease changes, which could timely monitor the therapeutic response and relapse trend.

Conclusion: The detection rate of ctDNA in CSF is higher than that in plasma. The dynamic monitoring of ctDNA in CSF has hint significance for therapeutic response of CNS lymphoma patients.