Genome-wide cfDNA fragmentation patterns in cerebrospinal fluid reflect medulloblastoma groups

Identifying molecular groups in medulloblastoma currently requires invasive biopsies for accurate diagnosis. We analyzed cerebrospinal fluid cell-free DNA (cfDNA) fragmentation patterns in 122 samples as a minimally-invasive alternative. Our analysis confirmed established group-specific copy number alterations and identified distinct fragmentation patterns for each group. Our integrated meta-classifier achieved high accuracy (mean-AUC 0.94) in distinguishing the four molecular groups, demonstrating cfDNA fragmentomics' potential for improving diagnosis and personalized treatment strategies.