Dataset Information

Risk stratification of H3 K27M-mutant diffuse midline gliomas based on anatomical locations: an integrated systematic review of individual participant data.

ABSTRACT:

Objective

The prognostic significance and genetic characteristics of H3 K27M-mutant diffuse midline gliomas (DMGs) in different anatomical locations requires further clarification. In this study, the authors integrated published data to investigate the differences between brainstem, thalamic, and spinal cord tumors.

Methods

PubMed and Web of Science databases were used to search for eligible articles. Studies were included if they provided individual patient data of H3 K27M-mutant DMGs with available tumor locations. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed to investigate the survival of each subgroup.

Results

Eight hundred four tumors were identified, including 467, 228, and 109 in the brainstem, thalamus, and spine, respectively. Brainstem tumors were primarily observed in young children, while patients with thalamic and spinal cord tumors afflicted older patients. The Ki-67 labeling index was highest in brainstem tumors. Compared to patients with brainstem tumors, those with thalamic (HR 0.573, 95% CI 0.463-0.709; p < 0.001) and spinal cord lesions (HR 0.460, 95% CI 0.341-0.621; p < 0.001) had a significantly better survival. When patients were stratified by age groups, superior overall survival (OS) of thalamic tumors was observed in comparison to brainstem tumors in young children and adolescents, whereas adult tumors had uniform OS regardless of anatomical sites. Genetically, mutations in HIST1H3B/C (H3.1) and ACVR1 genes were mostly detected in brainstem tumors, whereas spinal cord tumors were characterized by a higher incidence of mutations in the TERT promoter.

Conclusions

This study demonstrated that H3 K27M-mutant DMGs have distinct clinical characteristics, prognoses, and molecular profiles in different anatomical locations.

SUBMITTER: Vuong HG

PROVIDER: S-EPMC10193490 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

Risk stratification of H3 K27M-mutant diffuse midline gliomas based on anatomical locations: an integrated systematic review of individual participant data.

Vuong Huy Gia HG Le Hieu Trong HT Jea Andrew A McNall-Knapp Rene R Dunn Ian F IF

Journal of neurosurgery. Pediatrics 20220429 1

<h4>Objective</h4>The prognostic significance and genetic characteristics of H3 K27M-mutant diffuse midline gliomas (DMGs) in different anatomical locations requires further clarification. In this study, the authors integrated published data to investigate the differences between brainstem, thalamic, and spinal cord tumors.<h4>Methods</h4>PubMed and Web of Science databases were used to search for eligible articles. Studies were included if they provided individual patient data of H3 K27M-mutant ...[more]

PMID: 35535848

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Project description:Diffuse midline glioma (DMG), H3 K27M-mutant, is a new entity in the updated WHO classification grouping together diffuse intrinsic pontine gliomas and infiltrating glial neoplasms of the midline harboring the same canonical mutation at the Lysine 27 of the histones H3 tail.Two hundred and fifteen patients younger than 18 years old with centrally-reviewed pediatric high-grade gliomas (pHGG) were included in this study. Comprehensive transcriptomic (n = 140) and methylation (n = 80) profiling was performed depending on the material available, in order to assess the biological uniqueness of this new entity compared to other midline and hemispheric pHGG.Tumor classification based on gene expression (GE) data highlighted the similarity of K27M DMG independently of their location along the midline. T-distributed Stochastic Neighbor Embedding (tSNE) analysis of methylation profiling confirms the discrimination of DMG from other well defined supratentorial tumor subgroups. Patients with diffuse intrinsic pontine gliomas (DIPG) and thalamic DMG exhibited a similarly poor prognosis (11.1 and 10.8 months median overall survival, respectively). Interestingly, H3.1-K27M and H3.3-K27M primary tumor samples could be distinguished based both on their GE and DNA methylation profiles, suggesting that they might arise from a different precursor or from a different epigenetic reorganization.These differences in DNA methylation profiles were conserved in glioma stem-like cell culture models of DIPG which mimicked their corresponding primary tumor. ChIP-seq profiling of H3K27me3 in these models indicate that H3.3-K27M mutated DIPG stem cells exhibit higher levels of H3K27 trimethylation which are correlated with fewer genes expressed by RNAseq. When considering the global distribution of the H3K27me3 mark, we observed that intergenic regions were more trimethylated in the H3.3-K27M mutated cells compared to the H3.1-K27M mutated ones.H3 K27M-mutant DMG represent a homogenous group of neoplasms compared to other pediatric gliomas that could be further separated based on the type of histone H3 variant mutated and their respective epigenetic landscapes. As these characteristics drive different phenotypes, these findings may have important implication for the design of future trials in these specific types of neoplasms.

Dataset Information

Risk stratification of H3 K27M-mutant diffuse midline gliomas based on anatomical locations: an integrated systematic review of individual participant data.

Objective

Methods

Results

Conclusions

Publications

Risk stratification of H3 K27M-mutant diffuse midline gliomas based on anatomical locations: an integrated systematic review of individual participant data.

Similar Datasets

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