<b>Molecular mechanisms underpinning malignant vascular sarcomas</b>

<p dir="ltr">Vascular sarcomas are a rare and deadly type of tumor which arises from the endothelium that lines the inside of all blood and lymphatic vessels. As a group, these cancers are genetically diverse and the underlying molecular mechanisms are poorly understood. In order to develop novel therapeutic strategies for vascular sarcomas, further research into key dependencies that drive these cancers is needed. Epithelioid Hemangioendothelioma (EHE), is exclusively driven by one of two possible gene fusions, <i>YAP1::TFE3</i> or <i>TAZ::CAMTA1</i>. We generated transgenic <i>in vitro </i>models of EHE and observed a striking EndMT phenotype specific to the YT expressing endothelial cells. We determined that TFE3 donated domains are necessary to drive this phenotype, while TEAD binding is not. Our lab previously reported that <i>Dicer1 </i>deletion is sufficient to drive Angiosarcoma (AS) in mice. <i>Dicer1 </i>has multiple important functions, including DNA repair, antiviral response, and microRNA (miRNA) processing. To determine whether <i>Dicer1 </i>deletion drives AS though miRNA depletion, we generated a <i>Dgcr8 </i>KO mouse, which phenocopied <i>Dicer1 </i>deletion.</p>