Evidence map›Paper›PMID 39901723›Full record

ArticleNeuro-oncology2025

Loss of LDOC1 by chromatin compaction in mesenchymal tumor cells is required for PFA1 ependymoma growth.

Graziella Ribeiro de Sousa, Annaliese J Calzadilla, Enrique Grimaldo, Andrew M Donson, Lays Martin Sobral, Kendra M Jones, Tian Liu, Vladimir Amani, Sujatha Venkataraman, Nathan A Dahl and 8 more

Abstract read
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In one paragraph

Article in Neuro-oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Graziella Ribeiro de SousaRibeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.ORCID 0000-0003-1809-8539
Annaliese J CalzadillaDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Enrique GrimaldoDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Andrew M DonsonDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Lays Martin SobralDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Kendra M JonesDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Tian LiuDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Vladimir AmaniDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Sujatha VenkataramanDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.ORCID 0000-0002-1512-284X
Nathan A DahlDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Jean M Mulcahy LevyClinical Science Graduate Program, Anschutz Medical Campus, Aurora, Colorado, USA.
Tzu PhangDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Rajeev VibhakarClinical Science Graduate Program, Anschutz Medical Campus, Aurora, Colorado, USA.
Todd HankinsonDepartment of Neurosurgery, Anschutz Medical Campus, Aurora, Colorado, USA.
Michael HandlerDepartment of Neurosurgery, Anschutz Medical Campus, Aurora, Colorado, USA.
Elvis Terci ValeraRibeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
Nicholas K ForemanClinical Science Graduate Program, Anschutz Medical Campus, Aurora, Colorado, USA.
Andrea M GriesingerClinical Science Graduate Program, Anschutz Medical Campus, Aurora, Colorado, USA.ORCID 0000-0002-2831-1009

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
Colorado Clinical and Translational Sciences Institute (CCTSI)UM1TR004399 · NCATS · UNIVERSITY OF COLORADO DENVER · PI JANINE A HIGGINS, RONALD J. SOKOL · 2023 to 2026
$30.7M
Bruker 9.4T/ 20cm BioSpec MR Scanner for Colorado Animal Imaging Shared ResourcesS10OD023485 · OD · UNIVERSITY OF COLORADO DENVER · PI SERKOVA, NATALIE J. · 2017 to 2017
$2.0M
Epigenetic regulation of LDOC1 drives tumor biology in high risk ependymomaR01CA239302 · NCI · UNIVERSITY OF COLORADO DENVER · PI FOREMAN, NICHOLAS K · 2020 to 2024
$1.7M
NCATS NIH HHS UM1 TR004399NCI NIH HHS P30 CA046934NCI NIH HHS R01 CA239302NIH HHS S10 OD023485
6 · The paper itself

Abstract

backgroundPosterior fossa molecular subtype A (PFA) ependymoma occurs in young children and is the deadliest subtype of pediatric ependymoma. High-risk subtypes with chromosome 1q + and/or 6q- exhibit significantly poorer outcomes compared to wild-type PFA. However, 50% of wild-type PFA patients relapse and there is a high risk of gaining chromosome 1q at recurrence. We previously found constitutively active NF-κB, through loss of LDOC1, led to chronic IL-6 secretion and an overall immunosuppressive tumor microenvironment in the higher-risk wild-type PFA ependymoma subset (PFA1).

methodsIn this study, we delineate the mechanistic consequences of LDOC1 loss in PFA1, using our PFA ependymoma in vitro and in vivo models under normoxia and hypoxia conditions.

resultsWe noted chromatin compaction by H3K27me3 at the LDOC1 loci results in loss of LDOC1 gene expression. Restoration of LDOC1 was sufficient to reduce proliferation, NF-κB signaling, and a significant decrease in IL-6 secretion. Furthermore, tumors implanted with LDOC1-transduced cells in vivo were out competed by non-transduced cells, suggesting loss of LDOC1 is required for PFA tumor growth.

conclusionThese findings shed further light on the biology of PFA1 ependymoma and the role LDOC1 loss has on the tumor and immunobiology of high-risk pediatric ependymoma.

Indexed as

ChromatinEpendymomaInfratentorial NeoplasmsNuclear ProteinsAnimalsCell ProliferationHumansMiceNF-kappa BSignal TransductionTumor Cells, CulturedChromatinNF-kappa BNuclear Proteinsependymoma tumor growthhistonehypoxiaLDOC1posterior fossa

Identifiers

PMID39901723
PMCPMC12309711

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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.