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The Ewing sarcoma gene (EWS) has been implicated in pathogenesis of a large number of soft tissue sarcomas. Its normal functions are not clear as of today, although it has been implicated in cell signaling and RNA processing. Various chromosomal translocations may result in the EWS gene being aberrantly fused with other genes. These fusion genes may interfere with the normal cell cycle and act as oncogenes, rendering cells immortal and resulting in malignant growth. This article is an overview of neoplasms in which the Ewing sarcoma gene plays a pathogenetic role.
So what is the Ewing sarcoma gene?
The Ewing sarcoma gene, also known as EWS, is located on the long arm of chromosome 22. Its exact function in human cells remains unclear. It has been suggested that the EWS gene codes for a protein involved in RNA transcription and splicing. Other suggested roles include DNA repair, control of lymphocyte maturation, and involvement in meiosis and gametogenesis.
How does the Ewing sarcoma gene cause tumors?
By pairing the EWS gene with other genes as a result of chromosomal translocations, a number of fusion genes can be produced. These genes are not normally seen in human cells. The Ewing sarcoma gene in such a fusion product acts as a potent transcription factor, activating and/or enhancing the transcription of the other gene involved. This enhanced or aberrant transcription interferes with the normal cell cycle. The cells become immortal which clinically results in a tumor.
What tumors has the Ewing sarcoma gene been implicated in?
The following is the list of tumors in which genetic translocations involving the EWS gene play an important role. The bullet points list possible gene fusion products.
- Ewing sarcoma/primitive neuroectodermal tumor (PNET)
- EWS-FLI1
- EWS-ERG
- Desmoplastic small round cell tumor
- EWS-WT1
- Myxoid/round cell liposarcoma
- EWS-CHOP
- Clear cell sarcoma
- EWS-ATF1
- EWS-CREB1
- Myxoid chondrosarcoma
- EWS-CHN
So are all these tumors related to Ewing sarcoma?
No. All the tumors listed above are distinct clinical and pathological entities. The Ewing sarcoma gene is simply a genetic mechanism that is involved in their pathogenesis. Diagnostic features, as well as predicted clinical behavior, of the tumors listed above are beyond the scope of this article.
So what?
Are there any practical implications in identifying the translocations involving the EWS gene in these tumors? The answer is yes. Firstly, since many soft tissue tumors can look alike, identifying specific genetic alterations allows to arrive at the accurate diagnosis. Furthermore, in some instances such a translocation defines the tumor, i.e. the diagnosis can only be reliably made by documenting the tumor’s genetic makeup.
The utility of the genetic studies does not, however, stop here. In many instances specific genetic alterations allow to predict clinical behavior and even select targeted treatment agents.
Disclaimer. The content of this article is not intended as a substitute for medical advice. If any of the conditions mentioned above affects you, or you have questions about the materials presented here, it is best to consult your doctor.
