Liquid Biopsy Techniques for Central Nervous System Tumors

Liquid biopsy approaches for central nervous system tumours harness the analysis of tumour-derived material present in bodily fluids, predominantly cerebrospinal fluid and plasma. This non-invasive strategy centres on circulating tumour DNA, circulating tumour cells, extracellular vesicles and other biomolecules shed by malignancies of the brain and spinal cord. By capturing molecular alterations such as gene mutations, copy number changes and epigenetic markers, liquid biopsies permit diagnostic refinement, patient stratification and real-time monitoring of disease evolution. The blood–brain barrier imposes a unique challenge, often limiting the entry of tumour material into peripheral blood and highlighting cerebrospinal fluid as a richer reservoir of tumour biomarkers. Recent advances in sequencing technologies, digital PCR and vesicle isolation have greatly improved sensitivity and specificity, enabling the detection of low-frequency variants and tracking minimal residual disease. Beyond diagnostic applications, liquid biopsy techniques inform prognostic assessments, personalise treatment decisions and facilitate early detection of recurrence. The global significance of these innovations is underscored by their potential to reduce reliance on invasive neurosurgical procedures, broaden access to molecular diagnosis and deliver more precise therapeutic monitoring across diverse healthcare settings.

Research from Nature Portfolio

Studies exploring cerebrospinal fluid-derived circulating tumour DNA have established its superiority over plasma in reflecting the genomic landscape of central nervous system tumours. Early work demonstrated that massive parallel sequencing of cerebrospinal fluid ctDNA captures actionable somatic mutations and copy number alterations that are often undetectable in plasma, while longitudinal sampling correlates with tumour burden and treatment response. Further research has extended this paradigm to paediatric medulloblastoma, showing that cerebrospinal fluid ctDNA accurately recapitulates subgroup-specific alterations, uncovers intra-tumour heterogeneity and enables risk stratification. By enabling the detection of minimal residual disease and characterising genomic evolution at recurrence, these approaches inform refined clinical management and the design of tailored therapeutic strategies.

Liquid Biopsy Techniques for Central Nervous System Tumors publication trend

The graph below shows the total number of articles in liquid biopsy techniques for central nervous system tumors across all publications each year (not limited to Nature Index journals).

Technical terms

Cerebrospinal fluid (CSF): The clear fluid surrounding the brain and spinal cord, used as a medium for detecting tumour biomarkers.

Circulating tumour DNA (ctDNA): Fragments of DNA released by tumour cells into bodily fluids, carrying tumour-specific genetic alterations.

Extracellular vesicle (EV): Membrane-bound particles released by cells that transport proteins, nucleic acids and lipids reflective of the cell of origin.

Droplet digital PCR (ddPCR): A highly sensitive method for quantifying DNA variants by partitioning samples into thousands of droplets for parallel amplification.

Next-generation sequencing (NGS): High-throughput sequencing technology enabling comprehensive analysis of genetic alterations across the genome.

Copy number alteration (CNA): Variation in the number of copies of a genomic region, often indicative of oncogene amplification or tumour suppressor deletion.

Minimal residual disease (MRD): The small population of cancer cells that persist after treatment, which can be monitored via liquid biopsy to predict relapse.

References

1. Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma. Nature Communications (2015).
2. Circulating tumour DNA from the cerebrospinal fluid allows the characterisation and monitoring of medulloblastoma. Nature Communications (2020).
3. Seq-ing the SINEs of central nervous system tumors in cerebrospinal fluid. Cell Reports Medicine (2023).
4. Liquid biopsy of cerebrospinal fluid enables selective profiling of glioma molecular subtypes at first clinical presentation. Clinical Cancer Research (2023).
5. Extracellular vesicles in glioblastoma: a challenge and an opportunity. npj Precision Oncology (2024).