Gliomas are the most common brain tumor type in children and adolescents. The definitive diagnosis is made by surgery and the course of treatment is monitored using MRI (magnetic resonance imaging). However, this has not yet made it possible to track any biological changes during the treatment of the tumor. A group of researchers led by Johannes Gojo, an expert in childhood and adolescent brain tumors at the Department of Pediatrics and Adolescent Medicine, has now analyzed fragments of tumor DNA in the cerebrospinal fluid and blood of brain tumor patients. It was shown that the tumor-typical changes can be detected up to 40,000-fold diluted. These highly sensitive methods could be used for diagnosis but also for therapy monitoring in the clinic. “With the developed method, we can carry out and analyze up to 20,000 individual polymerase chain reactions on tumor DNA simultaneously in tiny droplets (ddPCR). This makes it possible to detect even the smallest amounts of tumor DNA,” says first author Sibylle Madlener, also from the Department of Pediatrics and Adolescent Medicine.
Proximity to the tumor is relevant
In the study, cell-free tumor DNA was extracted from liquid biopsies of 35 glioma patients and analyzed for specific mutations (H3F3A K27M and BRAF V600E). The samples were obtained from plasma and cerebrospinal fluid. The mutations were detected with high sensitivity and specificity using the sensitive droplet digital PCR (ddPCR) method. The sampling site of the cerebrospinal fluid proved to be particularly decisive: samples taken close to the tumor showed the best results.
The researchers observed that the mutations can not only be used diagnostically, but also contribute to monitoring the course of the disease and the response to therapy. “We were able to show that the corresponding markers (mutations) decrease in the cerebrospinal fluid and blood during targeted therapy, but become detectable again after the therapy is discontinued. In future, these markers can be used to individually control the therapy,” says study leader Johannes Gojo.
Significance for clinical practice
These results underline the potential of liquid biopsies as a less invasive alternative to conventional tissue biopsies but more importantly to guide therapy based on tracking tumor DNA. Liquid biopsies could revolutionize therapy monitoring, particularly for difficult-to-access tumors in the central nervous system. The findings of the study open up new perspectives for personalized medicine
Publication: Acta Neuropathologica
Detection of H3F3A K27M or BRAF V600E in liquid biopsies of brain tumor patients as diagnostic and monitoring biomarker: impact of tumor localization and sampling method.
Sibylle Madlener, Natalia Stepien, Daniel Senfter, Lisa Mayr, Anna Laemmerer, Cora Hedrich, Alicia Baumgartner, Daniela Lötsch-Gojo, Jaroslav Sterba, Petra Pokorna, Barbara Kiesel, Georg Widhalm, Franziska Eckert, Matthias Preusser, Karl Rössler, Amedeo Azizi, Andreas Peyrl, Thomas Czech, Christine Haberler, Irene Slavc, Gregor Kasprian, Christian Dorfer, Julia Furtner & Johannes Gojo.
doi: doi.org/10.1007/s00401-024-02842-7
https://link.springer.com/article/10.1007/s00401-024-02842-7