What are the genetic changes related to Ewing sarcoma ?
The most common mutation that causes Ewing sarcoma involves two genes, the EWSR1 gene on chromosome 22 and the FLI1 gene on chromosome 11. A rearrangement (translocation) of genetic material between chromosomes 22 and 11, written as t(11;22), fuses part of the EWSR1 gene with part of the FLI1 gene, creating the EWSR1/FLI1 fusion gene. This mutation is acquired during a person's lifetime and is present only in tumor cells. This type of genetic change, called a somatic mutation, is not inherited.  The protein produced from the EWSR1/FLI1 fusion gene, called EWS/FLI, has functions of the protein products of both genes. The FLI protein, produced from the FLI1 gene, attaches (binds) to DNA and regulates an activity called transcription, which is the first step in the production of proteins from genes. The FLI protein controls the growth and development of some cell types by regulating the transcription of certain genes. The EWS protein, produced from the EWSR1 gene, also regulates transcription. The EWS/FLI protein has the DNA-binding function of the FLI protein as well as the transcription regulation function of the EWS protein. It is thought that the EWS/FLI protein turns the transcription of a variety of genes on and off abnormally. This dysregulation of transcription leads to uncontrolled growth and division (proliferation) and abnormal maturation and survival of cells, causing tumor development.  The EWSR1/FLI1 fusion gene occurs in approximately 85 percent of Ewing sarcomas. Translocations that fuse the EWSR1 gene with other genes that are related to the FLI1 gene can also cause these types of tumors, although these alternative translocations are relatively uncommon. The fusion proteins produced from the less common gene translocations have the same function as the EWS/FLI protein.