ArticleiScience2020
Miswired Enhancer Logic Drives a Cancer of the Muscle Lineage.
Article in iScience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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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.
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Who cites it
37 citing papers in PubMed, 48 citations in OpenAlex.
- Article
- Fusion-positive rhabdomyosarcoma oncofusions share a common interactome.Nature communications · 2026Article
- CpG island density predicts CBP/p300 dependency across 3D chromatin clusters.bioRxiv : the preprint server for biology · 2026Article
- Comparative modes of chromatin engagement by PAX::FOXO1 fusions in rhabdomyosarcoma.bioRxiv : the preprint server for biology · 2026Article
- From bench to bedside: combining HDAC inhibitors with standard therapies in rhabdomyosarcoma treatment.Frontiers in cell and developmental biology · 2026Review
- Genetic and chromosomal dysregulations of progenitor cells in the etiology and pathogenesis of pediatric cancers.American journal of stem cells · 2026Review
- Structural variants in the 3D genome as drivers of disease.Nature reviews. Genetics · 2025Review
- Super-Enhancer DrivesAnimals : an open access journal from MDPI · 2025Article
- Rhabdomyosarcoma fusion oncoprotein initially pioneers a neural signature in vivo.Cell reports · 2025Article
- PROTACs coupled with oligonucleotides to tackle the undruggable.Bioanalysis · 2025Review
- Fusion oncogenes in rhabdomyosarcoma: model systems, mechanisms of tumorigenesis, and therapeutic implications.Frontiers in oncology · 2025Review
- Article
- Single cell transcriptomic profiling identifies tumor-acquired and therapy-resistant cell states in pediatric rhabdomyosarcoma.Nature communications · 2024Article
- Epigenetic determinants of fusion-driven sarcomas: paradigms and challenges.Frontiers in cell and developmental biology · 2024Article
- Myogenesis gone awry: the role of developmental pathways in rhabdomyosarcoma.Frontiers in cell and developmental biology · 2024Review
- PAX3-FOXO1 uses its activation domain to recruit CBP/P300 and shape RNA Pol2 cluster distribution.Nature communications · 2023Article
- PAX3-FOXO1 dictates myogenic reprogramming and rhabdomyosarcoma identity in endothelial progenitors.Nature communications · 2023Article
- Preclinical development of a chimeric antigen receptor T cell therapy targeting FGFR4 in rhabdomyosarcoma.Cell reports. Medicine · 2023Article
- The 3D chromatin landscape of rhabdomyosarcoma.NAR cancer · 2023Article
- Genomic and Epigenetic Changes Drive Aberrant Skeletal Muscle Differentiation in Rhabdomyosarcoma.Cancers · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
Core regulatory transcription factors (CR TFs) establish enhancers with logical ordering during embryogenesis and development. Here we report that in fusion-positive rhabdomyosarcoma, a cancer of the muscle lineage, the chief oncogene PAX3-FOXO1 is driven by a translocated FOXO1 super enhancer (SE) restricted to a late stage of myogenesis. Using chromatin conformation capture techniques, we demonstrate that the extensive FOXO1 cis-regulatory domain interacts with PAX3. Furthermore, RNA sequencing and chromatin immunoprecipitation sequencing data in tumors bearing rare PAX translocations implicate enhancer miswiring across all fusion-positive tumors. HiChIP of H3K27ac showed connectivity between the FOXO1 SE, additional intra-domain enhancers, and the PAX3 promoter. We show that PAX3-FOXO1 transcription is diminished when this network of enhancers is ablated by CRISPR. Our data reveal a hijacked enhancer network that disrupts the stepwise CR TF logic of normal skeletal muscle development (PAX3 to MYOD to MYOG), replacing it with an "infinite loop" enhancer logic that locks rhabdomyosarcoma in an undifferentiated stage.
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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.