An international team of researchers has developed a method that can be used to reliably diagnose common brain tumors in childhood and adolescence solely on the basis of cell-free tumor DNA in cerebrospinal fluid (CSF). The method combines an optimized enzymatic sequencing technique with a specially developed AI algorithm called “M-PACT”. The Hopp Children’s Cancer Center Heidelberg (KiTZ), the German Cancer Research Center (DKFZ), the Heidelberg Medical Faculty of Heidelberg University, Heidelberg University Hospital and St. Jude Children’s Research Hospital in Memphis, USA, were involved.

Until now, molecular precision diagnostics of brain tumors using liquid biopsy have not been reliably possible. The blood-brain barrier largely prevents the transfer of tumor DNA into the blood, and the amount of cell-free tumor DNA in the cerebrospinal fluid is also extremely low. So far, the material has not been sufficient for the methylation analysis of the tumor genome, which is the gold standard according to the WHO recommendation.

The team optimized a new enzymatic sequencing method to prepare even minimal amounts of cell-free DNA from cerebrospinal fluid in such a way that methylation signals can be reliably recorded. At the same time, it developed the AI algorithm M-PACT, which was specially trained on liquid biopsy data from brain tumors. In a validation study with 210 patient samples (around 20 different childhood brain tumor subtypes) and 58 non-malignant control samples, M-PACT achieved a high diagnostic specificity and sensitivity.

The algorithm not only provides a precise tumor classification, but also estimates the tumor burden and is therefore suitable for monitoring the course of the disease. In addition, it detects changes in disease-relevant genes as well as contributions of other cell types to CSF DNA content – information that could be relevant for immunotherapies or other targeted approaches in the future.

Further validation studies are required before widespread clinical application. The researchers are making the AI algorithm M-PACT freely accessible in order to invite international working groups to analyze their own liquid biopsy data. In the long term, the procedure could help to avoid some tissue removals and to make the diagnosis more precise before surgery – in order to initiate targeted therapy as quickly as possible. However, surgical tumor removal remains a central part of treatment.

Original Paper:

K.S. Smith et al. M-PACT leverages cell-free DNA methylomes to achieve robust classification of pediatric brain tumors In: Nature Cancer (online publication, February 17, 2026). DOI: 10.1038/s43018-026-01115-4

Editor: X-Press Journalistenbüro GbR

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