Ewing sarcoma is the second most common bone/soft tissue cancer in children and adolescents. Besides a few genetic mutations known to cause the primary tumour, little is known about what promotes the aggressive progression of Ewing sarcoma. Indeed, mutations that cause metastasis in Ewing sarcoma have remained utterly elusive. Children with metastatic Ewing sarcoma have a very poor outlook, with less than 20% survival rate. Sadly, this survival rate is further reduced to about 14% for patients with combined lung and bone/bone marrow metastases. Hence, there is an urgent need to identify the genetic causes of metastasis and to find and evaluate novel therapeutics that specifically target metastases in Ewing sarcoma. The principal aim of the proposed research is to discover the causes of metastasis in Ewing sarcoma using high-throughput DNA and RNA sequencing technologies and thereby to reveal new therapeutic options for fighting this grim childhood malignancy.