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.
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.
EWSR1 can join with many different partner genes. Each partner is linked to a specific tumor type. Examples include:
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.
Pathologists test for EWSR1 changes using molecular tests on the tumor tissue. The two most common methods are:
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.