New Paper Published in The Journal of Liquid Biopsy
A B S T R A C T
Background: Cerebrospinal fluid (CSF) is a relatively accessible biospecimen, and liquid biopsy (LBx) testing using
next-generation sequencing (NGS) provides actionable information on genomic abnormalities that can guide
clinical decisions and therapeutic selection. To evaluate the potential clinical utility of CSF LBx, we analyzed
real-world LB testing data from 1391 CSF samples.
Methods: CSF samples were submitted for clinical testing with various referring diagnoses, including primary
brain tumors and metastatic tumors. NGS testing of cell-free DNA and RNA (cfDNA and cfRNA) as well as cellular
RNA was performed using a targeted 302-gene DNA panel and a targeted RNA panel encompassing more than
1600 genes.
Results: Of all samples, 231 (16.6%) were completely negative for any abnormality, 69 (5.0%) showed findings
consistent with clonal hematopoiesis of indeterminate potential (CHIP), 2 (0.1%) demonstrated B-cell clonality
alone, and 14 (1.0%) showed chromosomal abnormalities without identified mutations. The remaining 1075
cases (78.4%) were positive for mutations with or without additional abnormalities, consistent with primary or
metastatic malignancy. cfRNA levels were extremely low in the majority of cases, with expression levels near
zero across a significant number of genes. Nevertheless, cellular and cfRNA were adequate for the detection of
fusion genes in 68 cases (4.9%) and CAR-T constructs in 5 cases (0.4%) of lymphoid neoplasms previously treated
with CAR-T therapy, including cases in which CAR-T cells were undetectable in peripheral blood.
Conclusions: These findings suggest that LBx using combined DNA and RNA NGS testing of CSF is a reliable
approach that yields potentially practice-changing clinical information.