DDIT3: Definition


Print this article

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.

What happens to DDIT3 in myxoid liposarcoma?

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.

How do pathologists test for DDIT3?

Pathologists can test for DDIT3 changes in several ways:

  • FISH. Fluorescence in situ hybridization (FISH) uses fluorescent probes to show whether the DDIT3 gene is broken. A DDIT3 break supports myxoid liposarcoma, regardless of the partner gene involved.
  • Sequencing. Next-generation sequencing (NGS) can identify DDIT3 and its exact partner gene, such as FUS::DDIT3.
  • Immunohistochemistry. Immunohistochemistry (IHC) can detect the DDIT3 protein in the nucleus of the tumor cells. Strong staining suggests a DDIT3 fusion is present, and this test is faster and less expensive than molecular testing.

What does a DDIT3 result mean?

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.

Questions to ask your doctor

  • Why was DDIT3 tested on my tumor?
  • Was a DDIT3 rearrangement or fusion found?
  • Which test was used, FISH, sequencing, or immunohistochemistry?
  • Was the partner gene identified?
  • Does the DDIT3 result confirm myxoid liposarcoma?
  • Was MDM2 also tested?
  • Does the DDIT3 result affect my treatment options?

Related articles on MyPathologyReport.com

A+ A A-
Was this article helpful?