ArticleCancer discovery2014
Comprehensive genomic analysis of rhabdomyosarcoma reveals a landscape of alterations affecting a common genetic axis in fusion-positive and fusion-negative tumors.
Article in Cancer discovery, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 481 papers, 2 of them syntheses that pooled it.
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Who cites it
481 citing papers in PubMed, 2 syntheses or guidelines pooled it, 771 citations in OpenAlex.
- The tumour microenvironment in paediatric rhabdomyosarcomas: a systematic review.Carcinogenesis · 2025Pooled it
- Alveolar rhabdomyosarcoma has superior response rates to vinorelbine compared to embryonal rhabdomyosarcoma in patients with relapsed/refractory disease: A meta-analysis.Cancer medicine · 2023Pooled it
- Phase II Study of Samotolisib in Children and Young Adults With Tumors Harboring Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Pathway Alterations: Pediatric MATCH APEC1621D.JCO precision oncology · 2024Trial
- NAPRT Expression and Epigenetic Regulation in Pediatric Rhabdomyosarcoma as a Potential Biomarker for NAMPT Inhibition.Molecular cancer therapeutics · 2026Article
- High-Risk Rhabdomyosarcomas Feature a Convergent Cell State.Cancer research · 2026Article
- MAPK-driven MYC/p21 axis controls senescence bypass and BCL-XL dependence in vincristine-resistant rhabdomyosarcoma.iScience · 2026Article
- Current Evidence for Circulating Tumor DNA in Sarcoma: Challenges and Opportunities for Clinical Application.Journal of surgical oncology · 2026Review
- Molecular Pathogenesis, Tumor Microenvironment and Health Disparities in Select Pediatric Solid Tumors: An Integrative Narrative Review.Diseases (Basel, Switzerland) · 2026Review
- Head and Neck Rhabdomyosarcoma in Children: An Otolaryngological Perspective on Diagnostic and Therapeutic Approaches.Current oncology reports · 2026Review
- MIR17HG Expression Is Transcriptionally Regulated by PAX3::FOXO1 and MYCN and is Necessary for Oncogenic Activity in Fusion-Positive Rhabdomyosarcoma.Molecular cancer research : MCR · 2026Article
- Catalase Defines Radiotherapy Resistance and a Therapeutic Vulnerability in Rhabdomyosarcoma.International journal of molecular sciences · 2026Article
- Paediatric Therapeutic Development Workshop on rhabdomyosarcoma.British journal of cancer · 2026Review
- PAX3::FOXO1-Targeting PROTAC Induces Myogenic Differentiation of Fusion-Positive Rhabdomyosarcoma Cells.Cancers · 2026Article
- Targeted antibody-drug conjugates for rhabdomyosarcoma and other FGFR4-expressing cancers.Cell reports. Medicine · 2026Article
- Unraveling the dual roles of MICAL2 in skeletal muscle physiology and fusion negative rhabdomyosarcoma tumor progression.Cell death & disease · 2026Article
- Core transcriptional regulatory circuitry identified from patient-derived tumor cells provides a specific vulnerability for rhabdomyosarcoma.Cell death & disease · 2026Article
- System for study of diverse cellular composition in alveolar rhabdomyosarcoma.Scientific reports · 2026Article
- Rhabdomyosarcoma Confined to the Bone Marrow: A Case Report and Literature Review.Current oncology (Toronto, Ont.) · 2026Review
- Multi-omics analyses identify EZH2 as a central driver in rhabdomyosarcoma radioresistance and highlight Tazemetostat as an effective radiosensitizer in vitro and in vivo.Cell death & disease · 2026Article
- Renaissance of farnesyltransferase inhibitors in cancer.Journal of translational medicine · 2026Review
421 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors at 13 institutions in 2 countries.
Funding
Abstract
unlabelledDespite gains in survival, outcomes for patients with metastatic or recurrent rhabdomyosarcoma remain dismal. In a collaboration between the National Cancer Institute, Children's Oncology Group, and Broad Institute, we performed whole-genome, whole-exome, and transcriptome sequencing to characterize the landscape of somatic alterations in 147 tumor/normal pairs. Two genotypes are evident in rhabdomyosarcoma tumors: those characterized by the PAX3 or PAX7 fusion and those that lack these fusions but harbor mutations in key signaling pathways. The overall burden of somatic mutations in rhabdomyosarcoma is relatively low, especially in tumors that harbor a PAX3/7 gene fusion. In addition to previously reported mutations in NRAS, KRAS, HRAS, FGFR4, PIK3CA, and CTNNB1, we found novel recurrent mutations in FBXW7 and BCOR, providing potential new avenues for therapeutic intervention. Furthermore, alteration of the receptor tyrosine kinase/RAS/PIK3CA axis affects 93% of cases, providing a framework for genomics-directed therapies that might improve outcomes for patients with rhabdomyosarcoma. SIGNIFICANCE: This is the most comprehensive genomic analysis of rhabdomyosarcoma to date. Despite a relatively low mutation rate, multiple genes were recurrently altered, including NRAS, KRAS, HRAS, FGFR4, PIK3CA, CTNNB1, FBXW7, and BCOR. In addition, a majority of rhabdomyosarcoma tumors alter the receptor tyrosine kinase/RAS/PIK3CA axis, providing an opportunity for genomics-guided intervention.
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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.