The prognostic significance of further genotyping H3G34 diffuse hemispheric gliomas
Huy Gia Vuong, Hieu Trong Le, Ian F. Dunn
Abstract
BACKGROUND: H3G34-mutant diffuse hemispheric glioma (DHG) is recognized as a new, distinct entity in the latest World Health Organization classification for central nervous system tumors and is associated with a particularly aggressive course. The authors performed a systematic review and pooled analysis to investigate the frequency of genetic events in these tumors and to determine whether these events were associated with survival trends. METHODS: Two electronic databases were accessed to search for relevant data. Included criteria were studies that had individual patient data on H3.3 G34-mutant gliomas. To analyze the impact of genetic events on overall survival, Kaplan-Meier analysis and Cox regression models were used, and corresponding hazard ratios and 95% confidence intervals were computed. RESULTS: In total, 20 studies with 257 H3G34-mutant DHGs were included for integrated analyses. The H3 glycine-to-valine (H3G34V) mutation showed a significantly worse prognosis than the glycine-to-arginine (H3G34R) mutation (median overall survival, 9.9 vs 14.8 months; hazard ratio, 3.040; 95% confidence interval, 1.208-7.651; P = .018), and this result remained statistically significant in the multivariate Cox regression model. Among H3G34 DHGs, TP53 mutation was the most common genetic alteration (94.9%), followed by ATRX alterations (87.5%), MGMT methylation (79.5%), and PDGFRA alterations (33.2%). The presence of PDGFRA amplification or EGFR amplification conferred poor survival. After adjusting for age and sex, these alterations were still independent indicators for adverse outcomes. CONCLUSIONS: The authors highlight the important role of molecular stratification of H3G34 DHGs, which may help refine our understanding of the natural history of this group of malignant tumors.