Evidence map›Paper›PMID 39812007›Full record

ArticleThe Journal of pathology2025

DNA methylation patterns are influenced by Pax3::Foxo1 expression and developmental lineage in rhabdomyosarcoma tumours forming in genetically engineered mouse models.

Wenyue Sun, Stephen M Hewitt, Hollis Wright, Charles Keller, Frederic G Barr

Abstract read
In one paragraph

Article in The Journal of pathology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

5 authors.

Wenyue SunLaboratory of Pathology, Center for Cancer Research, NCI, Bethesda, MD, USA.ORCID 0000-0003-1673-0895
Stephen M HewittLaboratory of Pathology, Center for Cancer Research, NCI, Bethesda, MD, USA.ORCID 0000-0001-8283-1788
Hollis WrightChildren's Cancer Therapy Development Institute, Hillsboro, OR, USA.
Charles KellerChildren's Cancer Therapy Development Institute, Hillsboro, OR, USA.ORCID 0000-0003-2505-7487
Frederic G BarrLaboratory of Pathology, Center for Cancer Research, NCI, Bethesda, MD, USA.ORCID 0000-0002-1051-7447

Funding

Epigenetic studies in rhabdomyosarcomaZIABC011423 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI BARR, FREDERIC · 2012 to 2025
$7.1M
Clinical & Mechanistic underpinnings to reducing PAX:FOXO1 for alveolar rhabdomyosarcomaR01CA258720 · NCI · CHILDREN'S CANCER THERAPY DEVELOP/INST · PI KELLER, CHARLES · 2021 to 2025
$1.5M
Pilot Project Investigating the PAX3-FOXO1 Protein in the Rare Disease RhabdomyosarcomaR03TR004666 · NCATS · CHILDREN'S CANCER THERAPY DEVELOP/INST · PI KELLER, CHARLES · 2023 to 2023
$140k
Carson Confronts CancerIntramural NIH HHS ZIA BC011423Joanna McAfee Childhood Cancer FoundationNCATS NIH HHS R03 TR004666NCI NIH HHS R01 CA258720NIH HHS 1ZIABC011423NIH HHS R01CA258720NIH HHS R03TR004666
6 · The paper itself

Abstract

Rhabdomyosarcoma (RMS) is a family of phenotypically myogenic paediatric cancers consisting of two major subtypes: fusion-positive (FP) RMS, most commonly involving the PAX3::FOXO1 fusion gene, formed by the fusion of paired box 3 (PAX3) and forkhead box O1 (FOXO1) genes, and fusion-negative (FN) RMS, lacking these gene fusions. In humans, DNA methylation patterns distinguish these two subtypes as well as mutation-associated subsets within these subtypes. To investigate the biological factors responsible for these methylation differences, we profiled DNA methylation in RMS tumours derived from genetically engineered mouse models (GEMMs) in which various driver mutations were introduced into different myogenic lineages. Our unsupervised analyses of DNA methylation patterns in these GEMM tumours yielded two major clusters, corresponding to high and no/low expression of Pax3::Foxo1, which mirrored the results for human FP and FN RMS tumours. Two distinct methylation-defined subsets were found for GEMM RMS tumours with no/low Pax3::Foxo1 expression: one subset enriched in Pax7 lineage tumours and a second subset enriched in myogenic factor 5 (Myf5) lineage tumours. Integrative analysis of DNA methylation and transcriptomic data in mouse and human RMS revealed a common group of differentially methylated and differentially expressed genes, highlighting a conserved set of genes functioning in both human RMS models and GEMMs of RMS. In conclusion, these studies provide insight into the roles of oncogenic fusion proteins and developmental lineages in establishing DNA methylation patterns in FP and FN RMS respectively. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Indexed as

DNA MethylationForkhead Box Protein O1PAX3 Transcription FactorRhabdomyosarcomaAnimalsCell LineageDisease Models, AnimalGene Expression Regulation, NeoplasticHumansMiceMice, TransgenicOncogene Proteins, FusionForkhead Box Protein O1Foxo1 protein, mouseOncogene Proteins, FusionPAX3 protein, humanPax3 protein, mousePAX3 Transcription FactorDNA methylationfusion genemouse modelmuscle developmentmutationPAX3::FOXO1rhabdomyosarcoma

Identifiers

PMID39812007
PMCPMC11794984

What Socratic holds

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Registered trials

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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 Socratic graph.