Instituto Valenciano de Microbiología

Masía El Romeral
Ctra. de Bétera a San Antonio Km. 0.3
46117 Bétera (Valencia)
Phone. 96 169 17 02
Fax 96 169 16 37
CIF B-96337217


Ewing 's sarcoma (Ewing sarcoma) - Genes EWSR1 and FLI1  

Ewing's sarcoma is a malignant tumor of bone or soft tissues such as cartilage or nerves. Several types of sarcoma of Ewing, including Ewing sarcoma of bone, Extraosseous Ewing's 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% of Ewing's sarcoma Ewing's sarcoma are bone, a bone tumor that usually develops in the femurs, pelvis, ribs or blades. Extraosseous Ewing's sarcoma tumors corresponds to soft tissue around the bone, such as cartilage. The peripheral primitive neuroectodermal tumor (pPNET) develops in nerve tissue and can be found in many parts of the body. Askin's tumor is a type of pPNET that develops in the chest.

Ewing sarcomas occur most often in children and young adults. People usually feel stiffness, pain, swelling or tenderness of the bone or surrounding tissue. Sometimes a tumor near the skin surface is perceived warm and soft to the touch. Often, affected children have a fever that does not go away. Ewing's sarcoma can cause bone weakening of the affected bone, and affected individuals may have a bone fracture without obvious cause. It is usual that causes Ewing's sarcoma metastasis, usually in the lungs, other bones or bone marrow.

The most frequent mutation responsible Ewing sarcoma involves two genes, the gene EWSR1 (EWS RNA binding protein 1), located on the long arm of chromosome 22 (22q12.2) and FLI1 (Fli-1 proto-oncogene, gene ETS transcription factor), located on the long arm of chromosome 11 (11q24.1-q24.3). A translocation of genetic material between chromosomes 22 and 11, t (11; 22) of the fused gene part EWSR1 FLI1, creating the fusion gene EWSR1 / FLI1. This mutation is acquired during a person 's life and is present only in tumor cells. This type of genetic change, called somatic mutation, not inherited.

The protein encoded from the gene fusion EWSR1 / FLI1, called EWS / FLI, has functions of proteins of both genes. The FLI protein encoded from FLI1, binds to DNA and regulates the transcription, which is the first step in encoding proteins from genes. FLI protein controls the growth and development of some cell types through regulation of the transcription of certain genes. The EWS protein encoded from EWSR1 gene, also regulates transcription. The EWS / FLI protein has DNA - protein FLI, and the function of regulating the transcription of the EWS protein binding function. It is believed that the EWS / FLI protein converts transcription of a variety of genes abnormally. This deregulation of transcription leads to uncontrolled proliferation and growth and maturation and survival of abnormal cells, resulting in tumor development.

The fusion gene EWSR1 / FLI1 occurs in approximately 85% of Ewing sarcomas. Translocations fuse the EWSR1 gene with other genes that are related FLI1 can also result in the development of these types of tumors, but these alternatives translocations are relatively rare. Fusion proteins encoded from less common translocations gene have the same function as the EWS / FLI protein.

Translocations involving the EWSR1 gene are involved in many types of soft tissue sarcoma. These translocations fuse the EWSR1 gene with one of several other genes. These other genes seem to determine the type of tumor that develops. The fusion gene EWSR1 / WT1 results in the development of tumor desmoplastic small round cell (DSRCT), a type of soft tissue sarcoma that occurs frequently in the abdomen. The fusion gene EWSR1 / ATF1 is involved in soft tissue sarcoma clear cell (or malignant melanoma of soft parts). In this type of cancer, tumors usually develop in tendons, especially in the knees, feet and ankles. A translocation which creates the fusion gene EWSR1 / NR4A3 extraskeletal myxoid is responsible chondrosarcoma, a rare type of soft tissue tumor that usually occurs in the lower part of the body, such as thighs or buttocks. The fusion gene EWSR1 / DDIT3 is in myxoid liposarcomas times in, although it is a rare cause of this cancer. Myxoid liposarcomas occur the fatty tissue in many parts of the body.

Ewing's sarcoma usually not inherited but arises from a somatic mutation in body cells that occurs after conception.  

Tests in IVAMI: in IVAMI perform detection of mutations associated with Ewing 's sarcoma, by complete PCR amplification of the exons of EWSR1 and FLI1, respectively, and subsequent sequencing genes.

Samples recommended: to not be an inherited mutation not debben peripheral blood samples used, but biopsy samples affected tissues.