ArticleActa neuropathologica communications2014
Increased 5-hydroxymethylcytosine and decreased 5-methylcytosine are indicators of global epigenetic dysregulation in diffuse intrinsic pontine glioma.
Article in Acta neuropathologica communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01106794 (Molecular Analysis of Samples From Patients With Diffuse Intrinsic Pontine Glioma and Brainstem Glioma), which is not on this map. Cited by 21 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Molecular Analysis of Samples From Patients With Diffuse Intrinsic Pontine Glioma and Brainstem Glioma
Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Bibliometric and visualization analysis in the field of epigenetics and glioma (2009-2024).Frontiers in oncology · 2024Pooled it
- LIN28B and Let-7 in Diffuse Midline Glioma: A Review.Cancers · 2023Review
- Review
- Article
- Histone Mark Profiling in Pediatric Astrocytomas Reveals Prognostic Significance of H3K9 Trimethylation and Histone Methyltransferase SUV39H1.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- Prostate Cancer Epigenetics: From Basic Mechanisms to Clinical Implications.Cold Spring Harbor perspectives in medicine · 2019Review
- Inhibition of enhancer of zest homologue 2 is a potential therapeutic target for high-MYC medulloblastoma.Neuropathology : official journal of the Japanese Society of Neuropathology · 2019Article
- MGMT Expression Contributes to Temozolomide Resistance in H3K27M-Mutant Diffuse Midline Gliomas and MGMT Silencing to Temozolomide Sensitivity in IDH-Mutant Gliomas.Neurologia medico-chirurgica · 2018Review
- MicroRNA-21 promotes cell proliferation by targeting tumor suppressor TET1 in colorectal cancer.International journal of clinical and experimental pathology · 2018Article
- Liquid biopsy for pediatric central nervous system tumors.NPJ precision oncology · 2018Review
- TET1 exerts its tumour suppressor function by regulating autophagy in glioma cells.Bioscience reports · 2017Article
- A driver role for GABA metabolism in controlling stem and proliferative cell state through GHB production in glioma.Acta neuropathologica · 2017Article
- Diffuse Intrinsic Pontine Glioma: New Pathophysiological Insights and Emerging Therapeutic Targets.Current neuropharmacology · 2017Review
- 5-Hydroxymethylcytosine localizes to enhancer elements and is associated with survival in glioblastoma patients.Nature communications · 2016Article
- The emerging insights into catalytic or non-catalytic roles of TET proteins in tumors and neural development.Oncotarget · 2016Review
- Recent Advances on the Molecular Pathology of Glial Neoplasms in Children and Adults.The Journal of molecular diagnostics : JMD · 2016Review
- Pharmacologic Wnt Inhibition Reduces Proliferation, Survival, and Clonogenicity of Glioblastoma Cells.Journal of neuropathology and experimental neurology · 2015Article
- Disrupting NOTCH Slows Diffuse Intrinsic Pontine Glioma Growth, Enhances Radiation Sensitivity, and Shows Combinatorial Efficacy With Bromodomain Inhibition.Journal of neuropathology and experimental neurology · 2015Article
- A standardized autopsy procurement allows for the comprehensive study of DIPG biology.Oncotarget · 2015Article
- Future Clinical Trials in DIPG: Bringing Epigenetics to the Clinic.Frontiers in oncology · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
introductionDiffuse intrinsic pontine glioma (DIPG) is a malignant pediatric brain tumor associated with dismal outcome. Recent high-throughput molecular studies have shown a high frequency of mutations in histone-encoding genes (H3F3A and HIST1B) and distinctive epigenetic alterations in these tumors. Epigenetic alterations described in DIPG include global DNA hypomethylation. In addition to the generally repressive methylcytosine DNA alteration, 5-hydroxymethylation of cytosine (5hmC) is recognized as an epigenetic mark associated with active chromatin. We hypothesized that in addition to alterations in DNA methylation, that there would be changes in 5hmC. To test this hypothesis, we performed immunohistochemical studies to compare epigenetic alterations in DIPG to extrapontine adult and pediatric glioblastoma (GBM) and normal brain. A total of 124 tumors were scored for histone 3 lysine 27 trimethylation (H3K27me3) and histone 3 lysine 9 trimethylation (H3K9me3) and 104 for 5hmC and 5-methylcytosine (5mC). An H-score was derived by multiplying intensity (0-2) by percentage of positive tumor nuclei (0-100%).
resultsWe identified decreased H3K27me3 in the DIPG cohort compared to pediatric GBM (p < 0.01), adult GBM (p < 0.0001) and normal brain (p < 0.0001). H3K9me3 was not significantly different between tumor types. Global DNA methylation as measured by 5mC levels were significantly lower in DIPG compared to pediatric GBM (p < 0.001), adult GBM (p < 0.01), and normal brain (p < 0.01). Conversely, 5hmC levels were significantly higher in DIPG compared to pediatric GBM (p < 0.0001) and adult GBM (p < 0.0001). Additionally, in an independent set of DIPG tumor samples, TET1 and TET3 mRNAs were found to be overexpressed relative to matched normal brain.
conclusionsOur findings extend the immunohistochemical study of epigenetic alterations in archival tissue to DIPG specimens. Low H3K27me3, decreased 5mC and increased 5hmC are characteristic of DIPG in comparison with extrapontine GBM. In DIPG, the relative imbalance of 5mC compared to 5hmC may represent an opportunity for therapeutic intervention.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.