Table 1.

Benefits and considerations for various biomarkers used for the detection of CNS tumors in CSF

Biomarker	Assay	Common Targets	Benefits	Considerations
cfDNA Mutations	• ddPCR • NGS	• AKT1 • BRAF • EGFR • IDH1 • KRAS • NF2 • NRAS • PIK3R1 • PRCH1 • PTEN • TERT • TP53	• Short half-life enables recurrence monitoring • Both driver and passenger mutations can be used • Specific mutations may be sensitive to adjuvant therapy	• Early stage tumors are challenging to detect •  Requires whole-exome sequencing or a large targeted panel due to diversity of mutations
cfRNA Expression	• Real-time PCR • ddPCR • Microarray • RNA-Seq	• miR-10b • miR-15b • miR-19 • miR-21 • miR-92a • miR-200 family	• miRNAs may target biologically relevant pathways	• Contamination with genomic DNA can hamper interpretation of results • May be limited to assessing a few targets at a time
cfDNA Methylation	• Methylation- specific PCR • Microarray • NGS	• MGMT • p16 • RASSF1A • TERT • THBS1 • TIMP-3	• Changes may precede mutations • Hypermethylation often occurs in tumor suppressor genes	• Challenging to assay for hypomethylation • Design of primers and probes is challenging due to low genome complexity after bisulfite conversion
Protein Concentration	• ELISA • Mass spectrometry	• AFP • B2M • bHCG • SPARCL1 • VEGF	• Inexpensive and straightforward to implement clinically • Represents functional changes at the protein level	• Low specificity due to confounding variables like inflammation and chronic disease