Abstract B008: Investigating the evolution of undifferentiated soft tissue sarcomas in a genetically engineered mouse model

Abstract

Abstract Undifferentiated soft tissue sarcomas (USTS) are an aggressive class of sarcomas with few effective treatment options. Because of the rarity of these sarcomas and the paucity of representative disease models, little is known about how they develop. We used single cell transcriptomics to study the initiation and evolution of an USTS in an autochthonous genetically engineered mouse model. We profiled multiple stages of tumor development and identified intermediary cell states that define sarcomagenesis. Interestingly, we identify two discrete evolutionary pathways that arise in parallel in the mouse model. To determine the human relevance of our findings, we are developing machine learning approaches to compare cell states between the mouse model with single-cell transcriptomes that we generated from patient-derived xenografts. This cross-species comparison will uncover core USTS cell states and define their ancestral state transitions. Our ultimate goal is to identify essential molecular features of USTS, which may represent entry points for future therapeutic strategies. Citation Format: Jason E. Chan, Jonathan Rub, Carleigh Sussman, Olivera Grbovic-huezo, William D. Tap, Cristina Antonescu, Sam Singer, Doron Betel, Tuomas Tammela. Investigating the evolution of undifferentiated soft tissue sarcomas in a genetically engineered mouse model [abstract]. In: Proceedings of the AACR Special Conference: Sarcomas; 2022 May 9-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(18_Suppl):Abstract nr B008.