A NEW cerebrospinal fluid (CSF) liquid biopsy approach could significantly improve how brain tumours are diagnosed, particularly in children, by using AI to analyse tiny amounts of tumour DNA found in cerebrospinal fluid. Researchers have developed a highly sensitive method that overcomes long-standing technical barriers and may reduce reliance on invasive surgical biopsies.
Central nervous system tumours, including many paediatric brain cancers, are difficult to diagnose and monitor because tumour tissue is not always easy or safe to obtain. CSF liquid biopsy offers a minimally invasive alternative by analysing tumour-derived DNA fragments circulating in the fluid surrounding the brain and spinal cord. However, low DNA levels and limited genetic mutations have previously restricted its clinical usefulness.
Using Methylation Patterns to Improve CSF Liquid Biopsy
The new workflow moves beyond traditional mutation-based testing by focusing on DNA methylation, a chemical pattern that reflects tumour cell identity. Researchers developed a deep-learning model, called M-PACT, that can classify central nervous system tumours from extremely small amounts of cell-free DNA.
In benchmarking and validation cohorts of embryonal brain tumours, the CSF liquid biopsy approach achieved classification accuracies of 92% and 88%, respectively, despite using subnanogram quantities of DNA. Importantly, the model also performed well in non-embryonal tumours, samples with balanced genomes, and non-malignant CSF.
More Than Tumour Classification
Beyond diagnosis, the CSF liquid biopsy workflow enabled additional clinically relevant analyses. These included methylation-based cellular deconvolution, which helps identify the cellular composition of samples, and sensitive detection of copy-number variations, a key feature in many brain tumours.
Together, these capabilities suggest the approach could support more comprehensive tumour profiling from a single fluid sample, even when tumour burden is low.
Implications for Paediatric Neuro-Oncology
For children with brain tumours, reducing the need for repeat surgeries or tissue biopsies could be particularly valuable. A reliable CSF liquid biopsy may support earlier diagnosis, help distinguish primary from secondary malignancies, and potentially allow closer disease monitoring over time.
The researchers emphasise that these findings represent a foundational step rather than a ready-to-use clinical test. Prospective clinical trials will be needed to confirm performance in real-world settings and to determine how the method can best be integrated into routine care.
If validated, this methylation-based CSF liquid biopsy approach could mark a significant advance in precision diagnostics for central nervous system tumours, offering a safer and more informative option for patients and clinicians alike.
Reference
Smith KS et al. M-PACT leverages cell-free DNA methylomes to achieve robust classification of pediatric brain tumors. Nat Cancer. 2026; DOI:10.1038/s43018-026-01115-4.
