H3G34-Mutant Gliomas-A Review of Molecular Pathogenesis and Therapeutic Options

The 2021 World Health Organization Classification of Tumors of the Central Nervous System reflected advances in understanding of the roles of oncohistones in gliomagenesis with the introduction of the H3.3-G34R/V mutant glioma to the already recognized H3-K27M altered glioma, which represent the diagnoses of pediatric-type diffuse hemispheric glioma and diffuse midline glioma, respectively. Despite advances in research regarding these disease entities, the prognosis remains poor. While many studies and clinical trials focus on H3-K27M-altered-glioma patients, those with H3.3-G34R/V mutant gliomas represent a particularly understudied population. Thus, we sought to review the current knowledge regarding the molecular mechanisms underpinning the gliomagenesis of H3.3-G34R/V mutant gliomas and the diagnosis, treatment, long-term outcomes, and possible future therapeutics.

Automated summary

The 2021 World Health Organization Classification of Tumors of the Central Nervous System introduced the H3.3-G34R/V mutant glioma alongside the already recognized H3-K27M altered glioma, reflecting advances in understanding the roles of oncohistones in gliomagenesis. However, the prognosis remains poor for patients with these disease entities and the H3.3-G34R/V mutant gliomas are particularly understudied. Further research is needed to explore the molecular mechanisms underlying gliomagenesis and develop effective diagnosis, treatment, and future therapeutics.