Peer-reviewed article
OTHR-39. Extraneural spreading of a diffuse leptomeningeal glioneuronal tumor in a child: patient-derived models show sensitivity to vinblastin and trametinib
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Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001This is a medical case report describing the development of laboratory models from a rare brain tumor in a child. The models were used to test drug sensitivity in the laboratory. While it involves a child patient, the work is fundamentally about tumor biology and drug testing rather than child well-being, health outcomes, or development.
Key points
Limitations
This document is a clinical case study focused on tumor biology and in vitro/in vivo drug testing. It does not evaluate interventions for child well-being, health outcomes, or development.
Abstract
Abstract Diffuse leptomeningeal glioneuronal tumors (DLGNT) are rare neoplasms of the central nervous system. We describe the generation of patient-derived models from a DLGNT that metastasized to the peritoneal cavity via a ventriculoperitoneal shunt in a child. The original tumor contained a KIAA1549:BRAF fusion with a chromosome 1p deletion and corresponded with methylation subclass DLGNT-MC-2 From a sample of ascitic fluid, metastatic tumoral cells could be extracted and expanded ex vivo into a long-term cell culture model. This patient-derived cell line (PDCL) showed mixed morphological phenotypes and expressed MAP2 and SYP. The KIAA1549:BRAF fusion was preserved and the PDCL still corresponded to the original methylation subclass DLGNT-MC-2. Whole-genome sequencing showed additional mutations potentially contributing to the malignant behavior of the tumor. Cytotoxic assays performed on the PDCL indicated high sensitivity to vinblastine and trametinib (MEK-inhibitor) and intermediate sensitivity to DRD/ClpP-modulators. The PDCL underwent viral transduction to induce GFP-fLux positivity and was intraperitoneally injected into immunocompromised mice. A mouse model could be generated, with the growth of a peritoneal tumor in a localized manner. The cells grown from the mouse tumor were again put into culture and were afterwards subjected to the same treatments as the PDCL. This confirmed a similar profile, with high sensitivity to vinblastin and trametinib and an intermediate sensitivity to the DRD/ClpP-modulators. In conclusion, we were able to generate patient-derived models from a metastatic DLGNT, which recapitulate the molecular characteristics of the original tumor. The models showed high sensitivity to vinblastin and targeted therapy with MEK-inhibition, but further studies are necessary to define the adequate treatment for this kind of tumor.