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Genetics Home Reference: your guide to understanding genetic conditions
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Ewing sarcoma

Reviewed May 2012

What is Ewing sarcoma?

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.

How common is Ewing sarcoma?

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).

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.

Related Chromosome(s)

Changes involving these chromosomes are associated with Ewing sarcoma.

  • chromosome 11
  • chromosome 22

Related Gene(s)

Changes in these genes are associated with Ewing sarcoma.

  • ERG
  • ETV1
  • ETV4
  • EWSR1
  • FEV
  • FLI1
  • FUS

Can Ewing sarcoma be inherited?

This condition is generally not inherited but arises from a mutation in the body's cells that occurs after conception. This alteration is called a somatic mutation.

Where can I find information about diagnosis or management of Ewing sarcoma?

These resources address the diagnosis or management of Ewing sarcoma and may include treatment providers.

  • Cancer.Net: Ewing Family of Tumors - Childhood: Diagnosis (http://www.cancer.net/cancer-types/ewing-sarcoma-childhood/diagnosis?sectionTitle=Diagnosis)
  • Cancer.Net: Ewing Family of Tumors - Childhood: Treatment (http://www.cancer.net/cancer-types/ewing-sarcoma-childhood/treatment-options?sectionTitle=Treatment)
  • Genetic Testing Registry: Ewing's sarcoma (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0553580)
  • MedlinePlus Encyclopedia: Ewing Sarcoma (http://www.nlm.nih.gov/medlineplus/ency/article/001302.htm)

You might also find information on the diagnosis or management of Ewing sarcoma in Educational resources (http://www.ghr.nlm.nih.gov/condition/ewing-sarcoma/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/ewing-sarcoma/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about Ewing sarcoma?

You may find the following resources about Ewing sarcoma helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for Ewing sarcoma?

  • Ewing family of tumors
  • Ewing's sarcoma
  • Ewing's tumor
  • Ewing tumor
  • tumor of the Ewing family

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Ewing sarcoma?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding Ewing sarcoma?

bone marrow ; cancer ; cartilage ; cell ; chromosome ; DNA ; fever ; fusion gene ; gene ; metastasize ; mutation ; osteosarcoma ; pelvis ; peripheral ; proliferation ; protein ; rearrangement ; sarcoma ; somatic mutation ; tissue ; transcription ; translocation ; tumor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/8164678?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/9488465?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/7517940?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/8516324?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/8246959?dopt=Abstract)
  • Ohno T, Rao VN, Reddy ES. EWS/Fli-1 chimeric protein is a transcriptional activator. Cancer Res. 1993 Dec 15;53(24):5859-63. (http://www.ncbi.nlm.nih.gov/pubmed/7503813?dopt=Abstract)
  • 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. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21872822?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: May 2012
Published: July 7, 2014