ArticleNature genetics2015
Chimeric EWSR1-FLI1 regulates the Ewing sarcoma susceptibility gene EGR2 via a GGAA microsatellite.
Article in Nature genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 1 of them a synthesis that pooled it.
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Who cites it
115 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Genome-wide contribution of common short-tandem repeats to Parkinson's disease genetic risk.Brain : a journal of neurology · 2023Pooled it
- A Practical Compass to Biological Digital Resources and Omics Integration in Ewing Sarcoma.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Germline Variation and Somatic Alterations in Ewing Sarcoma.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Analysis of Regulatory DNA Sequences by Dual-Luciferase Reporter Assays in Ewing Sarcoma.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Fusion Oncoprotein EWSR1::FLI1 Invades Nucleosomes at Consensus ETS Motifs and GGAA Microsatellites.bioRxiv : the preprint server for biology · 2026Article
- Spatially resolved profiling of steroid nuclear receptors reveals a role for the disordered N-terminal domains in genome targeting and AP-1 interaction.Genome research · 2026Article
- Article
- Long-read analysis of tetrameric microsatellites with vmwhere supports GGAA repeat length-dependent chromatin state association in Ewing sarcoma.bioRxiv : the preprint server for biology · 2026Article
- Integrative screening identifies functional variants and VNTRs underlying GWAS signals at the 5p15.33 multi-cancer susceptibility locus.medRxiv : the preprint server for health sciences · 2026Article
- Genome-wide association study meta-analysis identifies susceptibility loci informing Ewing sarcoma etiology and potential mechanisms of risk.medRxiv : the preprint server for health sciences · 2026Article
- Suppressing the Aberrant Transcriptional Functionality of EWS::FLI1 Oncoprotein by Designer polyQ Fusions with Its Homologous Peptides.Biomedicines · 2026Article
- A Statistical Framework to Infer the Mutation Model of Tandem Repeat Variants.bioRxiv : the preprint server for biology · 2026Article
- The hegemonic EWSR1::ETS oncoprotein overrules core regulatory circuitry principles in Ewing sarcoma.NPJ precision oncology · 2025Article
- Small round cell sarcoma tumoroid biobank reveals CIC::DUX4 sarcoma vulnerability to MCL-1 inhibition.Nature communications · 2025Article
- Mutations of short tandem repeats explain abundant trait heritability in Arabidopsis.Genome biology · 2025Article
- Intrinsically disordered regions as facilitators of the transcription factor target search.Nature reviews. Genetics · 2025Review
- Targeting metastasis in paediatric bone sarcomas.Molecular cancer · 2025Review
- Structure and cooperative formation of a FLI1 filament on contiguous GGAA DNA sites.Nucleic acids research · 2025Article
- Re-envisioning genetic predisposition to childhood and adolescent cancers.Nature reviews. Cancer · 2025Review
- Ewing Sarcoma in the Pediatric Population: Predictors of Survival Within the United States.Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews · 2024Article
55 more citing papers are in PubMed but not listed here.
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Abstract
Deciphering the ways in which somatic mutations and germline susceptibility variants cooperate to promote cancer is challenging. Ewing sarcoma is characterized by fusions between EWSR1 and members of the ETS gene family, usually EWSR1-FLI1, leading to the generation of oncogenic transcription factors that bind DNA at GGAA motifs. A recent genome-wide association study identified susceptibility variants near EGR2. Here we found that EGR2 knockdown inhibited proliferation, clonogenicity and spheroidal growth in vitro and induced regression of Ewing sarcoma xenografts. Targeted germline deep sequencing of the EGR2 locus in affected subjects and controls identified 291 Ewing-associated SNPs. At rs79965208, the A risk allele connected adjacent GGAA repeats by converting an interspaced GGAT motif into a GGAA motif, thereby increasing the number of consecutive GGAA motifs and thus the EWSR1-FLI1-dependent enhancer activity of this sequence, with epigenetic characteristics of an active regulatory element. EWSR1-FLI1 preferentially bound to the A risk allele, which increased global and allele-specific EGR2 expression. Collectively, our findings establish cooperation between a dominant oncogene and a susceptibility variant that regulates a major driver of Ewing sarcomagenesis.
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