Contemporary Precision Stratification and Prognostic Features of Primary Gliomas in a Southern Chinese Population

With the significant transformation in the classification, risk stratification, and therapy standards for gliomas in recent years, we sought to reintegrate clinical data, whole-exome sequencing data, and magnetic resonance imaging data from glioma patients to further analyze their impact on overall survival. We identified 798 primary gliomas: 355 glioblastomas, 179 IDH1/2-mutant astrocytomas, 135 oligodendrogliomas, and 129 other IDH1/2-wild-type gliomas. Kaplan-Meier analysis revealed that our cohort showed significantly prolonged survival compared to the CGGA/TCGA cohorts (median: 85.2, 60.4, and 50.5 months; P < 0.0001). Molecular reclassification criteria yielded altered final histopathologic classification for 23.7% of gliomas. Molecular alterations differ among glioma subtypes. Among the 5 tumorigenic pathways analyzed, glioblastomas exhibited the highest average number of activated pathways (mean: 2.17), followed by astrocytomas (mean: 1.40) and oligodendrogliomas (mean: 0.42). In one glioma subtype, upstream and downstream gene activations in the same pathway are mutually exclusive. In this large-scale Chinese cohort, we first confirmed a strong link between tumor location and molecular subtype: Frontal gliomas had IDH1/2 mutations in 63.5% of cases, while temporal (80.3%) and thalamic/basal ganglia gliomas (90.4%) were predominantly IDH1/2-wild-type. Age stratification confirmed these patterns: 74.7% of frontal gliomas in younger patients (<46 years) had IDH1/2 mutations versus 91.4% of temporal and 100% of thalamic/basal ganglia tumors in older patients (≥46 years) being IDH1/2-wild-type. Contemporary molecular criteria modified diagnoses in ~25% of cases. Contemporary glioma cohorts showed prolonged survival outcomes compared to historical cohorts. An association between anatomic localization and molecular subtypes was also established in this Chinese glioma cohort.