EWSR1: Definition


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EWSR1 is a gene that makes a protein involved in reading and processing the cell’s genetic instructions. Its name stands for Ewing sarcoma breakpoint region 1 because researchers first discovered it in Ewing sarcoma. In some tumors, EWSR1 breaks and joins with a different gene, creating an abnormal gene called a fusion. Testing for EWSR1 helps pathologists diagnose several types of sarcoma and other tumors.

An EWSR1 result is a test result, not a diagnosis. The same EWSR1 change can occur in very different tumors, so its meaning depends on the other gene it has joined. This article explains what EWSR1 does, which tumors have EWSR1 changes, and what an EWSR1 result in your pathology report means.

What happens to EWSR1 in tumors?

EWSR1 sits on chromosome 22. In certain tumors, a break occurs in EWSR1 and in another gene, and the two broken pieces join together. This event is called a translocation or rearrangement. The result is a fusion gene that makes an abnormal protein.

The fusion protein switches on genes that should normally be off. This drives tumor growth. The change happens only in the tumor cells. It is not inherited and cannot be passed on to children.

Which tumors have EWSR1 changes?

EWSR1 can join with many different partner genes. Each partner is linked to a specific tumor type. Examples include:

  • Ewing sarcoma. Most cases of Ewing sarcoma have a fusion between EWSR1 and a gene called FLI1. Fewer cases have a fusion between EWSR1 and ERG.
  • Desmoplastic small round cell tumor. This rare cancer, which usually starts in the abdomen of young people, has a fusion between EWSR1 and a gene called WT1.
  • Clear cell sarcoma. This rare tendon and soft tissue cancer has a fusion between EWSR1 and a gene called ATF1 or, less often, CREB1.
  • Extraskeletal myxoid chondrosarcoma. This rare soft tissue cancer usually has an EWSR1-NR4A3 fusion.
  • Myoepithelial tumors. Many soft-tissue myoepitheliomas have EWSR1 fusions with one of several partner genes.
  • Other tumors. EWSR1 fusions are also found in some cases of myxoid liposarcoma, angiomatoid fibrous histiocytoma, and some salivary gland tumors.

Because EWSR1 is involved in so many tumors, finding an EWSR1 change does not, on its own, confirm Ewing sarcoma or any other single diagnosis.

How do pathologists test for EWSR1?

Pathologists test for EWSR1 changes using molecular tests on the tumor tissue. The two most common methods are:

  • FISH. Fluorescence in situ hybridization (FISH) uses glowing probes to show whether the EWSR1 gene has been broken apart. FISH can confirm EWSR1 rearrangement, but it usually cannot identify the partner gene.
  • Sequencing. Next-generation sequencing (NGS), especially RNA-based tests, can identify both EWSR1 and the exact partner gene. This gives the pathologist more specific information.

What does an EWSR1 result mean?

A positive result means the tumor cells have an EWSR1 rearrangement or fusion. Your report may say “EWSR1 rearrangement detected,” “positive for EWSR1 rearrangement,” or name the specific fusion, such as “EWSR1::FLI1 fusion.”

The pathologist interprets the result together with what the tumor looks like under the microscope, where it is in the body, and the results of other tests. When the partner gene is known, it usually points to a specific diagnosis. When only FISH has been done, additional testing may be needed to identify the partner.

A negative result means no EWSR1 rearrangement was found. It makes some diagnoses less likely. However, some tumors, such as certain Ewing sarcomas, have a fusion involving a similar gene called FUS instead of EWSR1.

Questions to ask your doctor

  • Why was EWSR1 tested on my tumor?
  • Was an EWSR1 rearrangement found?
  • Was the partner gene identified?
  • What type of test was used, FISH or sequencing?
  • Does the EWSR1 result confirm my diagnosis?
  • Are any other tests needed to confirm the diagnosis?
  • Does the EWSR1 result affect my treatment options?
  • Could my family members have this genetic change?

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