Distinct Clinicogenomic Contexts of BRAF ‐Altered Gliomas and Glioneuronal Tumors: A Nationwide Real‐World Study

BRAF alterations occur across diverse gliomas and glioneuronal tumors, but their alteration-specific clinicogenomic contexts in real-world cancer genomic profiling cohorts remain incompletely characterized. We analyzed BRAF-altered brain tumors registered in the Japanese Center for Cancer Genomics and Advanced Therapeutics database from June 2019 to March 2026. Operational diagnostic harmonization was performed using available clinicopathological and genomic information. Grade-stratified analyses focused on BRAF p.V600E-positive gliomas and glioneuronal tumors. Among 413 BRAF-altered brain tumors, 344 were classified as gliomas and glioneuronal tumors after harmonization. Within this cohort, the major alteration contexts included BRAF p.V600E-positive tumors (n = 166), KIAA1549::BRAF fusion-positive tumors (n = 60), amplification-only tumors (n = 15), and tumors with other BRAF alterations (n = 109), with overlap in a subset. KIAA1549::BRAF fusion-positive tumors were mainly associated with low-grade glioma contexts, particularly pilocytic astrocytoma. Amplification-only tumors showed marked enrichment of MET alterations, all representing MET amplification, together with frequent EGFR and TP53 co-alterations, supporting a receptor tyrosine kinase-amplified, copy-number-rich context. Among 118 grade-evaluable BRAF p.V600E-positive gliomas and glioneuronal tumors, CDKN2A/B homozygous deletion and TP53/ATRX alterations were enriched in higher-grade groups, and high-grade tumors showed increased tumor mutational burden, although hypermutator phenotypes were rare. BRAF alteration classes define distinct clinicogenomic contexts in gliomas and glioneuronal tumors. These findings highlight both the opportunities and methodological challenges of nationwide real-world cancer genomic profiling datasets in central nervous system tumor research.