利用游离DNA（cfDNA）和RNA（cfRNA）诊断和监测原发及转移性中枢神经系统肿瘤

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.