Mentor Name: Corinne Linardic

Rhabdomyosarcoma (RMS) is a cancer related to the skeletal muscle lineage, and the most common soft tissue sarcoma of childhood. The fusion-positive subtype of RMS (FP-RMS), classified based on its expression of the fusion oncoprotein PAX3::FOXO1, has remained one of the most difficult to cure childhood cancers. To gain insight into FP-RMS biology and eventually identify novel therapeutic targets, our group has been interested in understanding the mechanisms that support FP-RMS cell state plasticity. This is important because plasticity at least partially underlies the resistance to treatment seen so commonly in children and adolescents with FP-RMS. In addition, recent single cell RNAseq data has identified a subset of FP-RMS cells with a neuronal signature, but the significance of this is unknown. Thus far, we have found that loss of function of a specific transcriptional repressor that associates with PAX3::FOXO1 initiates the conversion of myoblastic FP-RMS cells to a neurogenic phenotype. However, we have yet to fully characterize these switched cells, and need to assess the expression of the stemness marker SOX2, since SOX2 is important for neuronal cell identity and has been described in the literature as part of normal neural crest and embryonic development. The research goal of this POST program is to assess the expression and role of the stemness marker SOX2 in the cell state switch that we have found in FP-RMS.