Fiche publication
Date publication
août 2026
Journal
Acta neuropathologica
Auteurs
Membres identifiés du Cancéropôle Est :
Pr HARLE Alexandre
,
Pr MERLIN Jean-Louis
Tous les auteurs :
Gehin W, Merlin MS, Harle A, Merlin JL
Lien Pubmed
Résumé
Pediatric central nervous system tumors remain a leading cause of cancer-related mortality in children, while their diagnosis, risk stratification, and therapeutic management increasingly depend on integrated molecular characterization. However, representative tumor tissue is often difficult to obtain because of tumor location, surgical risk, limited biopsy material, and the impracticality of repeated sampling during disease evolution. Cerebrospinal fluid (CSF) has therefore emerged as a particularly informative liquid biopsy compartment for many CNS malignancies, enriched in tumor-derived cell-free DNA and, for tumors in contact with the CSF spaces, more directly reflective of intracranial tumor biology than plasma; its yield nonetheless varies with tumor biology and anatomical proximity to CSF pathways. Here, we review the evidence supporting CSF cell-free DNA sequencing as an emerging extension of molecular neuropathology in pediatric CNS tumors. Targeted next-generation sequencing, low-pass whole-genome sequencing, methylation-based classifiers, and nanopore sequencing now enable complementary assessment of somatic mutations, copy number alterations, epigenetic tumor class, and longitudinal tumor burden from low-input pediatric CSF samples. Recent studies have moved the field beyond analytical proof of concept towards defined clinical scenarios, including molecular diagnosis when biopsy is infeasible, molecular staging of high-CSF-shedding tumors, minimal residual disease monitoring in medulloblastoma and other embryonal tumors, and clarification of ambiguous radiological progression. CSF-based sequencing does not replace tissue neuropathology, but provides a liquid molecular layer that can complement, extend, or in selected situations partially substitute tissue-based diagnosis. Its broader adoption now depends on workflow standardization, assay-specific reporting standards, external quality assurance, and prospective evidence that CSF-guided decisions improve patient outcomes.
Mots clés
Cell-free DNA, Cerebrospinal fluid, Methylation profiling, Minimal residual disease, Molecular neuropathology, Next-generation sequencing, Pediatric CNS tumors
Référence
Acta Neuropathol. 2026 08 10;152(1):
