Heterogeneity in the gene regulatory landscape of leiomyosarcoma

Soft-tissue sarcomas are group of rare, tremendously heterogeneous, and highly aggressive malignancies. Characterizing inter-tumor heterogeneity is crucial for selecting suitable sarcoma therapy, as the presence of diverse molecular subgroups of patients can be associated with disease outcome or response to treatment. While cancer subtypes are often characterized by differences in gene expression, the mechanisms that drive these differences are generally unknown. We therefore set out to model the regulatory mechanisms driving sarcoma heterogeneity. We subtyped soft-tissue sarcomas based on patient-specific, genome-wide gene regulatory networks and found pronounced regulatory heterogeneity in leiomyosarcoma—one of the most common soft-tissue sarcomas subtypes that arises in smooth muscle tissue. Overall design: ATAC-seq was performed on four leiomyosarcoma cell lines, including SK-UT-1, SK-UT1-B, MES-SA and SK-LMS-1. Each cell lines had three replicates.