Abstract 6456: Investigating neuronal signatures in treated fusion positive rhabdomyosarcoma

Abstract Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue sarcoma with features of skeletal muscle and can be split into two subtypes: fusion positive and fusion negative. Fusion positive-rhabdomyosarcoma (FP-RMS) have a higher likelihood of resurgence over three years after treatment, and patients with recurrent disease experience dismal outcomes with a survival rate under 20%. While long-term treatment responses for this subtype have remained elusive, recent studies have been able to identify the presence of a neuronal cell state in FP-RMS, which has not been observed in FP-RMS cell lines. Furthermore, it is unknown if FP-RMS cell lines can recapitulate this neuronal state. We predicted chemotherapy exposure to be a driving stimulus for lineage transition of FP-RMS cells and examined the neuronal gene expression of chemotherapy-treated FP-RMS cell lines using quantitative PCR (qPCR) and TaqMan Array Cards. We find that treated FP-RMS cell lines induce a dose-dependent increase of expression in neuronal cell markers, and a dose-dependent decrease of expression in muscle cell markers, which suggests the induction of a new cell state in FP-RMS cell lines. For future direction, we will utilize RNA-seq and single cell multi-omics to examine molecular determinates of this linage plasticity. These findings collectively will support future studies by serving as an in vitro model for the study of lineage plasticity in childhood cancer. Citation Format: Sophie Q. Burke, Roketa Henry, Angelica Oliveras Alsina, Avanthika Balu, Elisabet Olsen, Anand Patel. Investigating neuronal signatures in treated fusion positive rhabdomyosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6456.