Fli1 (Friend leukemia integration 1 transcription factor) was identified in the mouse genome as a viral integration site common to 2 retroviruses involved in virus-induced leukemias and lymphomas. The mouse Fli1 region is close to the centromere of chromosome 9 [
14], while human FLI1 gene is located on chromosome 11q23-q24. It lies on a fragment flanked on the centromeric side, by the translocation breakpoint in acute lymphoblastic leukemia-associated t(4;11)(q21;q23) [
15] and on the telomeric side in Ewing sarcoma-associated t(11;22)(q24;q12) breakpoint [
16]. Several breakpoints have been described for EWSR1 and FLI1 in soft tissue tumors. The most common are EWSR1 exon 7 and FLI1 exon 6 (defined as Type I), EWSR1 exon 7 and FLI1 exon 5 (defined as Type II), EWSR1 exon 10 and FLI1 exon 6 (defined as Type III), and EWSR1 exon 7 and FLI1 exon 7 (defined as Type IV). Many other translocations have been described, such as EWSR1 exon 7 and FLI1 exon 8, EWSR1 exon 8 and FLI1 exon 6, EWSR1 exon 9 and FLI1 exon 4, EWSR1 exon 9 and FLI1 exon 7, EWSR1 exon 10 and FLI1 exon 5 and EWSR1 exon 10 and FLI1 exon 8 [
3]. The fusion transcript EWSR1/FLI1, as well as many other chimeric proteins, interferes with several molecular pathways, influencing the development and progression of this tumor. In particular, the interaction of the chimeric transcript with important mediators of cell cycle has been described. EWSR1/FLI1 results in an upregulation of c-Myc and a downregulation of p57KIP2 [
17]. In addition, the fusion transcript is able to inhibit the transcriptional activity of p53 [
18]. EWSR1/FLI1 also determines an upregulation of GLI, altering the molecular pathways associated with it [
19]. It has been recently demonstrated, using cellular models, that EWSR1/FLI1 is able to block the ability of Runx2 in order to induce osteoblast differentiation, responsible of Ewing tumor pathogenesis [
20]. Recent studies have showed the strong association between chimeric transcripts and microRNA activity. EWS/FLI1 is able to modulate miRNA 145 controlling cell differentiation [
21]. Additionally, deregulation of let7a is strongly related to EWS/FLI1 production [
22]. The fusion transcript EWSR1/FLI1 is present in more than 90 % of the Ewing sarcomas, and in the related group of peripheral primitive neuroectodermal tumor (pPNET) [
23], in rhabdomyosarcoma [
24], in neuroblastoma [
25] and in giant cell tumor of bone [
26].