青年および若年成人（AYA）における神経膠腫の治療パラダイムの再定義：分子分類のための集団ベースのエビデンス

Gliomas represent the second most common malignancy and leading cause of cancer death in adolescents and young adults (AYA; aged 15-39 years), yet their molecular landscape remains incompletely characterized. This study aims to characterize the molecular landscape of primary gliomas in AYA by integrating multi-omics data.

We recruited a cohort of patients with histopathologically diagnosed primary gliomas. The data encompassed clinical, imaging, histopathological, genomic testing data, and survival outcome data. The correlations of clinicopathological features, molecular characteristics, and anatomical heterogeneity with prognosis were evaluated.

Adult-type gliomas (66.2%) predominated but pediatric-type gliomas constituted 23.6%, exhibiting distinct clinicopathological profiles: pediatric-type tumors harbored frequent H3.3 (51.9%), TP53 (35.1%), and BRAF mutations (22.8%), while adult-type showed IDH (72.5%) and TP53 alterations (48.6%). IDH and H3.3/BRAF mutations were mutually exclusive. Anatomically, midline involvement (18.3%) correlated with younger age (≤25 years, P=0.019), frontal gliomas were predominantly IDH-mutations (58.3%), and midline tumors were enriched H3.3 K27M mutations (52.5%). Survival analysis revealed H3.3 K27M-mutant high-grade gliomas had the poorest prognosis (median survival: 16 months), whereas BRAF-driven low-grade gliomas showed favorable outcomes. Pediatric-type molecular alterations are enriched in AYA gliomas. IDH-wildtype tumors require sequencing to detect pediatric-type drivers (e.g., H3.3/BRAF mutations).

The treatment strategies for AYA gliomas should be determined by molecular classification rather than age-based stratification. Adult-type and pediatric-type gliomas exhibit distinct biological and driver profiles. AYA gliomas exhibit significant molecular-anatomical heterogeneity, with specific anatomical regions demonstrating enrichment of molecular signatures.