REVIEW article

Front. Oncol.

Sec. Pediatric Oncology

Volume 15 - 2025 | doi: 10.3389/fonc.2025.1570070

This article is part of the Research TopicCurrent Status And Recent Advances In Preclinical Models For Rare CancersView all 7 articles

Fusion Oncogenes in Rhabdomyosarcoma: Model Systems, Mechanisms of Tumorigenesis, and Therapeutic Implications

Provisionally accepted
  • 1Nationwide Children's Hospital, Columbus, United States
  • 2The Ohio State University, Columbus, Ohio, United States

The final, formatted version of the article will be published soon.

Rhabdomyosarcoma (RMS) contributes to 3% of all childhood cancers with roughly 400-500 cases diagnosed each year in the United States. The World Health Organization classifies rhabdomyosarcoma into four histological subtypes which include alveolar, embryonal, spindle-cell and pleomorphic. The primary genetic drivers in a subset of alveolar and spindle-cell histological subtypes are gene fusions. This review explores the fusion oncogenes identified in RMS such as PAX-and NCOA2-based fusions, along with discussing studies defining fusion oncogene biology and tumorigenic mechanisms. Focus areas include data around transformation events and progression along with dysregulated biological processes. Furthermore, we summarize model systems, ranging from cell to animal models, that have been implemented to study fusion oncogenes identified in RMS. With the constant identification of novel fusion oncogenes, this review also emphasizes the need for genetically characterizing RMS tumors and rapidly developing new model systems. These models are critical to study fusion oncogene activity and delineating key regulatory players and potential therapeutic targets that suppress tumorigenesis. The identification of RMS fusion oncogenes and integration with animal and cell culture models will help identify conserved molecular targets, optimize therapeutic approaches, and ultimately improve clinical outcomes for children with RMS.

Keywords: Pediatric sarcomas, PAX3/7::FOXO1, VGLL2::NCOA2, skeletal muscle, Oncogenic drivers, Animal Models

Received: 02 Feb 2025; Accepted: 30 May 2025.

Copyright: © 2025 Sankhe, Hall and Kendall. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Genevieve C Kendall, Nationwide Children's Hospital, Columbus, United States

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