DDIT3 is a gene that makes a protein involved in how cells respond to stress. In tumors, DDIT3 is best known for its role in myxoid liposarcoma, a cancer of fat tissue. In almost every myxoid liposarcoma, DDIT3 joins another gene, creating an abnormal fusion gene. DDIT3 is also known as CHOP.
A DDIT3 result is a test result, not a diagnosis. Testing for DDIT3 helps pathologists confirm a diagnosis of myxoid liposarcoma and separate it from other tumors that look similar. This article explains what DDIT3 does, how pathologists test for it, and what a DDIT3 result in your pathology report means.
DDIT3 sits on chromosome 12. In myxoid liposarcoma, a break occurs in DDIT3 and another gene, and the two broken pieces join. In a small number of cases, the partner is EWSR1.
The fusion gene makes an abnormal protein that prevents immature fat cells from maturing normally and drives tumor growth. The change happens only in the tumor cells. It is not inherited and cannot be passed on to children.
Pathologists can test for DDIT3 changes in several ways:
A positive molecular result means the tumor cells have a DDIT3 rearrangement or fusion. Your report may say “DDIT3 rearrangement detected” or name the fusion, such as “FUS::DDIT3.” In a fatty tumor with the right appearance, this confirms a diagnosis of myxoid liposarcoma.
A negative result makes myxoid liposarcoma unlikely. Other tumors that can look similar under the microscope, such as intramuscular myxoma and some lipomas with myxoid change, do not have DDIT3 fusions.
DDIT3 sits close to another gene called MDM2. In well-differentiated liposarcoma and dedifferentiated liposarcoma, extra copies of MDM2 are made, and extra copies of DDIT3 are sometimes made along with it. This is called amplification, and it is different from a DDIT3 fusion. Amplification can cause a positive DDIT3 immunohistochemistry result, so the pathologist considers the whole picture before making a diagnosis.