Vascular tumors of bone and related lesions: from gene fusions to tumor models

Abstract

Chromosomal translocations can be found in 15-20% of mesenchymal tumors, and are relatively more frequent among vascular tumors. To date, recurrent chromosomal translocations have been identified in hemangioma (HE), epithelioid hemangioma (EH), retiform/composite hemangioendothelioma, pseudomyogenic hemangioendothelioma (PHE), TFE3-rearranged hemangioendothelioma, and epithelioid hemangioendothelioma (EHE). When it comes to treatment of these often locally aggressive rarely metastasizing tumors, there are no or limited therapeutic options available other than surgery, which can cause problems when tumors are aggressively growing and are multifocal. The latter is often seen in vascular tumors. Therefore, it is all the more important to map out the uncharted territories of genotypes that underpin these conditions and to understand the underlying molecular mechanisms. This knowledge can improve therapeutic strategies and effectiveness. The aim of the thesis is divided into two parts - 1. explore promiscuity of gene fusions (i.e. EWSR1::NFATC2) in vascular tumors and related lesions, and 2. develop methods to study the underlying molecular mechanisms of genetic alterations and potential therapeutic strategies in vascular tumors.