ArticleActa neuropathologica communications2025
H3F3B p.K27I-mutant diffuse midline glioma is a distinct subtype of H3K27-altered diffuse midline glioma.
Article in Acta neuropathologica communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Clarification of the published survival analysis in H3F3B p.K27I-mutant diffuse midline glioma.Acta neuropathologica communications · 2026Article
- Structural landscape of H3K27me3 recognition by protein domains and their potential for inhibition.The Journal of biological chemistry · 2026Review
- Prevalence and Clinicoradiopathological Characterization of H3 K27-Altered Diffuse Midline Gliomas in Adults-A Retrospective Observational Study.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Article
- H3K27ME3 loss in diffuse midline gliomas lacking H3K27M or EZHIP expressions, a potential diagnostic pitfall!Acta neuropathologica · 2026Article
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Abstract
H3K27-altered diffuse midline glioma (DMG) is a fatal disease, including four subtypes H3.3-mutant, H3.1/H3.2-mutant, H3-wildtype with EZHIP overexpression, and EGFR-mutant. H3F3B, another gene encoding histone H3.3 in addition to H3F3A, was ever reported to be mutated in DMGs. However, the clinical and molecular characteristics of H3F3B-mutant DMGs is yet understood. The clinical and radiological information of 9 patients with H3F3B-mutant DMG were retrospectively collected. Tumor specimens underwent DNA methylation profiling and next-generation sequencing. All tumors harbored somatic H3F3B p.K27I mutation. Average patient age was 46 ± 6.86 years, 6 tumors located in spinal cord, 5 tumors involved brainstem and 2 arose in the thalamus. Immunohistochemistry showed these tumors exhibited completely or mosaic-like loss of H3K27me3 expression. Unsupervised t-distributed stochastic neighbor embedding (t-SNE) analysis of DNA methylation profiles showed that H3F3B-mutant DMGs formed a unique methylation cluster separate from other gliomas with H3K27me3 loss and DMGs with canonical histone H3 mutation. PPM1D and NF1 were frequently mutated in H3F3B-mutant DMGs. Survival analysis showed that H3F3B-mutant DMGs had poor prognosis comparable to H3K27M-mutant DMGs. Taken together, H3F3B mutation also cause a loss of H3K27 trimethylation in DMGs and result in poor prognosis. The distinct characteristics of DNA methylation and mutational spectrum between H3F3B-mutant DMGs and canonical H3K27M-mutant DMGs might suggest divergent underlying mechanism of gliomagenesis.
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