Zebrafish rhabdomyosarcoma

Abstract

In vivo models of Rhabdomyosarcoma (RMS) have proven instrumental in understanding the development and progression of this devastating pediatric sarcoma. Both vertebrate and invertebrate model systems have been developed to study the tumor biology of both embryonal (ERMS) and alveolar (ARMS) RMS subtypes. Zebrafish RMS models have been particularly amenable for highthroughput studies to identify drug targetable pathways because of their short tumor latency, ease of ex vivo manipulation and conserved tumor biology. The transgenic KRASG12D-induced ERMS model allows for molecular and cellular characterization of distinct tumor cell subpopulations including the tumor propagating cells. Comparative genomic approaches have also been utilized in zebrafish ERMS to identify conserved candidate driver genes. Recent advances in zebrafish genome engineering have further enabled the ability to probe the functional significance of potential driver genes. Using the unique strengths of the zebrafish model organisms with the wealth of cellular and molecular tools currently available, zebrafish RMS models provide a powerful in vivo system for which to study RMS tumorigenesis.