ArticleActa neuropathologica communications2020
Global activation of oncogenic pathways underlies therapy resistance in diffuse midline glioma.
Article in Acta neuropathologica communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- Diffuse Midline Gliomas: Clinical, Diagnostic, and Therapeutic Perspectives.Biomedicines · 2026Review
- Alternative splicing in pediatric central nervous system tumors highlights oncofetal candidateNeuro-oncology pediatrics · 2026Article
- Disrupting PDGFRA-driven immune evasion in glioma: vaccine-based strategies on the horizon.Frontiers in oncology · 2026Review
- Germline analysis of an international cohort of pediatric diffuse midline glioma patients.Neuro-oncology · 2025Article
- Characterization of aberrant splicing in pediatric central nervous system tumors revealsbioRxiv : the preprint server for biology · 2025Article
- Effects of combination therapy of a CDK4/6 and MEK inhibitor in diffuse midline glioma preclinical models.PloS one · 2025Article
- Rational combination platform trial design for children and young adults with diffuse midline glioma: A report from PNOC.Neuro-oncology · 2024Article
- Article
- Adult glioblastoma with Lynch syndrome-associated mismatch repair deficiency forms a distinct high-risk molecular subgroup.Free neuropathology · 2024Article
- Decoding Diffuse Midline Gliomas: A Comprehensive Review of Pathogenesis, Diagnosis and Treatment.Cancers · 2023Review
- Radiotherapy and radio-sensitization in H3CNS neuroscience & therapeutics · 2023Review
- Article
- Histone H3-wild type diffuse midline gliomas with H3K27me3 loss are a distinct entity with exclusive EGFR or ACVR1 mutation and differential methylation of homeobox genes.Scientific reports · 2023Article
- Patterns of care in adult histone mutant gliomas: Results of an international survey.Neuro-oncology practice · 2022Article
- STAT3 is a biologically relevant therapeutic target in H3K27M-mutant diffuse midline glioma.Neuro-oncology · 2022Article
- Germline MUTYH mutations and high-grade gliomas: Novel evidence for a potential association.Genes, chromosomes & cancer · 2022Article
- Novel neoplasms associated with syndromic pediatric medulloblastoma: integrated pathway delineation for personalized therapy.Cell communication and signaling : CCS · 2022Article
- Glioma Stem Cells in Pediatric High-Grade Gliomas: From Current Knowledge to Future Perspectives.Cancers · 2022Review
- Pharmaco-proteogenomic profiling of pediatric diffuse midline glioma to inform future treatment strategies.Oncogene · 2022Review
- Development of immunotherapy for high-grade gliomas: Overcoming the immunosuppressive tumor microenvironment.Frontiers in medicine · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diffuse midline gliomas (DMGs) are aggressive pediatric brain tumors with dismal prognosis due to therapy-resistant tumor growth and invasion. We performed the first integrated histologic/genomic/proteomic analysis of 21 foci from three pontine DMG cases with supratentorial dissemination. Histone H3.3-K27M was the driver mutation, usually at high variant allele fraction due to recurrent chromosome 1q copy number gain, in combination with germline variants in ATM, FANCM and MYCN genes. Both previously reported and novel recurrent copy number variations and somatic pathogenic mutations in chromatin remodeling, DNA damage response and PI3K/MAPK growth pathways were variably detected, either in multiple or isolated foci. Proteomic analysis showed global upregulation of histone H3, lack of H3-K27 trimethylation, and further impairment of polycomb repressive complex 2 by ASXL1 downregulation. Activation of oncogenic pathways resulted from combined upregulation of N-MYC, SOX2, p65/p50 NF-κB and STAT3 transcription factors, EGFR, FGFR2, PDGFRα/β receptor tyrosine kinases, and downregulation of PHLPP1/2, PTEN and p16/INK4A tumor suppressors. Upregulation of SMAD4, PAI-1, CD44, and c-SRC in multiple foci most likely contributed to invasiveness. This integrated comprehensive analysis revealed a complex spatiotemporal evolution in diffuse intrisic pontine glioma, recommending pontine and cerebellar biopsies for accurate populational genetic characterization, and delineated common signaling pathways and potential therapeutic targets. It also revealed an unsuspected activation of a multitude of oncogenic pathways, including cancer cell reprogramming, explaining the resistance of DMG to current therapies.
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.