Ewing sarcoma is a cancerous tumor that occurs in bones or soft tissues, such as cartilage or nerves. There are several types of Ewing sarcoma, including Ewing sarcoma of bone, extraosseous Ewing sarcoma, peripheral primitive neuroectodermal tumor (pPNET), and Askin tumor. These tumors are considered to be related because they have similar genetic causes. These types of Ewing sarcoma can be distinguished from one another by the tissue in which the tumor develops. Approximately 87 percent of Ewing sarcomas are Ewing sarcoma of bone, which is a bone tumor that usually occurs in the thigh bones (femurs), pelvis, ribs, or shoulder blades. Extraosseous (or extraskeletal) Ewing sarcoma describes tumors in the soft tissues around bones, such as cartilage. pPNETs occur in nerve tissue and can be found in many parts of the body. A type of pPNET found in the chest is called Askin tumor.

Ewing sarcomas most often occur in children and young adults. Affected individuals usually feel stiffness, pain, swelling, or tenderness of the bone or surrounding tissue. Sometimes, there is a lump near the surface of the skin that feels warm and soft to the touch. Often, children have a fever that does not go away. Ewing sarcoma of bone can cause weakening of the involved bone, and affected individuals may have a broken bone with no obvious cause.

It is common for Ewing sarcoma to spread to other parts of the body (metastasize), usually to the lungs, to other bones, or to the bone marrow.

Approximately 3 per 1 million children each year are diagnosed with a Ewing sarcoma. It is estimated that, in the United States, 250 children are diagnosed with one of these types of tumor each year. Ewing sarcoma accounts for about 1.5 percent of all childhood cancers, and it is the second most common type of bone tumor in children (the most common type of bone cancer is called osteosarcoma).

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.

Genetic Testing Information

• Genetic Testing Registry: Ewing sarcoma

Genetic and Rare Diseases Information Center

• Skeletal Ewing sarcoma

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Clinical Trials

• ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

• EWING SARCOMA; ES

Scientific Articles on PubMed

• PubMed

• Bailly RA, Bosselut R, Zucman J, Cormier F, Delattre O, Roussel M, Thomas G, Ghysdael J. DNA-binding and transcriptional activation properties of the EWS-FLI-1 fusion protein resulting from the t(11;22) translocation in Ewing sarcoma. Mol Cell Biol. 1994 May;14(5):3230-41. doi: 10.1128/mcb.14.5.3230-3241.1994. Citation on PubMed or Free article on PubMed Central
• Bertolotti A, Melot T, Acker J, Vigneron M, Delattre O, Tora L. EWS, but not EWS-FLI-1, is associated with both TFIID and RNA polymerase II: interactions between two members of the TET family, EWS and hTAFII68, and subunits of TFIID and RNA polymerase II complexes. Mol Cell Biol. 1998 Mar;18(3):1489-97. doi: 10.1128/MCB.18.3.1489. Citation on PubMed or Free article on PubMed Central
• Kim SK, Park YK. Ewing sarcoma: a chronicle of molecular pathogenesis. Hum Pathol. 2016 Sep;55:91-100. doi: 10.1016/j.humpath.2016.05.008. Epub 2016 May 28. Citation on PubMed
• Mao X, Miesfeldt S, Yang H, Leiden JM, Thompson CB. The FLI-1 and chimeric EWS-FLI-1 oncoproteins display similar DNA binding specificities. J Biol Chem. 1994 Jul 8;269(27):18216-22. Citation on PubMed
• May WA, Gishizky ML, Lessnick SL, Lunsford LB, Lewis BC, Delattre O, Zucman J, Thomas G, Denny CT. Ewing sarcoma 11;22 translocation produces a chimeric transcription factor that requires the DNA-binding domain encoded by FLI1 for transformation. Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5752-6. doi: 10.1073/pnas.90.12.5752. Citation on PubMed or Free article on PubMed Central
• May WA, Lessnick SL, Braun BS, Klemsz M, Lewis BC, Lunsford LB, Hromas R, Denny CT. The Ewing's sarcoma EWS/FLI-1 fusion gene encodes a more potent transcriptional activator and is a more powerful transforming gene than FLI-1. Mol Cell Biol. 1993 Dec;13(12):7393-8. doi: 10.1128/mcb.13.12.7393-7398.1993. Citation on PubMed or Free article on PubMed Central
• Ohno T, Rao VN, Reddy ES. EWS/Fli-1 chimeric protein is a transcriptional activator. Cancer Res. 1993 Dec 15;53(24):5859-63. Citation on PubMed
• Sankar S, Lessnick SL. Promiscuous partnerships in Ewing's sarcoma. Cancer Genet. 2011 Jul;204(7):351-65. doi: 10.1016/j.cancergen.2011.07.008. Citation on PubMed or Free article on PubMed Central