[Functional genomics of Ewing sarcoma].
Ewing sarcoma is a highly aggressive bone or soft-tissue tumor mostly occurring in children and adolescents. Conventional multi-modal therapies are associated with considerable acute and chronic toxicity. Thus, more effective and in particular less toxic therapeutic strategies are urgently required. Despite the fact that Ewing sarcoma is characterized by specific EWSR1-ETS gene fusions, the resulting fusion oncoproteins are not suitable for targeted therapy due to their low immunogenicity and the ubiquitous expression of their constituents. However, functional genomics revealed several EWSR1-ETS target genes, which are only minimally expressed in normal tissues, and which could serve as surrogate-targets for (immuno-)therapeutic approaches. Moreover, functional genomic analyses yielded first mechanistic explanations for the relatively high incidence of Ewing sarcoma in Europeans, and first studies are exploring the value of circulating free DNA and/or exosomal mRNA of EWSR1-ETS fusion oncogenes as minimal-residual-disease markers in Ewing sarcoma. This review summarizes key contributions to these aspects and gives a perspective on their medical relevance.