The prognostic significance of further genotyping H3G34 diffuse hemispheric gliomas

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.

Systematic review of diffuse hemispheric glioma, H3 G34-mutant: Outcomes and associated clinical factors

“…A study recently published by Vuong et al aimed to highlight the role of genetic events and molecular alterations in prognosis for G34-DHG. 35 Our studies demonstrated different median OS with theirs being slightly lower at 14.4 months compared to 17.3 months in our study. Of note, their study also determined that G34V-mutant tumors had significantly worse OS when compared to G34R-mutant tumors.…”

“…Also, their study demonstrated the role of EGFR amplification on reducing patient survival, not assessed in our study, and should be further evaluated. 35 …”

Identification of Prognostic Signature of Necroptosis-Related lncRNAs and Molecular Subtypes in Glioma

“…The latest 2021 WHO Classification of Tumors of the Central Nervous System integrated histological features and molecular phenotypes of tumors and further proposed the new tumor classification criteria, which focus on advancing the application of molecular diagnosis in the classification of CNS tumors [2]. In recent decades, molecular markers, including the isocratic dehydrogenase (IDH) mutation, the codeletion of chromosome arms 1p and 19q (1P/19q codeletion), and the H3 G34 mutant, have been demonstrated that play a significant role in the classification, grading, prognosis and treatment of gliomas [3][4][5]. However, these markers have limited sensitivity and accuracy [6].…”

Utility of arterial spin labeling for objective assessment of intratumoral microvessels in diffuse hemispheric glioma, H3 G34R-mutant: A case report and literature review

“…The prognosis of DHG, H3 G34m is better than that of glioblastoma, with a median progression-free survival of 9 months and a median overall survival of 18-22 months [1 , 3 , 12] . The relatively favorable prognosis has been attributed to a high frequency (74%-79.5%) of MGMT methylation associated with the sensitivity to alkylating agents in patients with DHG, H3 G34m [3 , 17] . Although MGMT methylation could not be assessed for this case, the patient showed good therapeutic response and continued progression-free survival for 20 months after starting treatments including bevacizumab.…”