T-Cell Receptor Gene Rearrangement
Note: this site is for informational purposes only. To view test results or book a test, use the NHS app in England or contact your GP.
A T‑cell receptor gene rearrangement test detects changes (rearrangements) in T‑cell receptor genes using samples such as blood, bone marrow or tissue obtained by biopsy. It is used to help diagnose T‑cell lymphomas and to evaluate whether abnormal T‑cell populations are present or if disease has persisted or returned after treatment.
Why get tested?
To help diagnose a T‑cell lymphoma; sometimes to detect and evaluate residual cancer cells
When to get tested?
When a doctor thinks that you may have a T‑cell lymphoma; when a doctor would like to assess whether treatment has been effective and/or whether lymphoma has recurred
Sample required?
A bone marrow, tissue such as a lymph node (biopsy), or body fluid sample collected by your doctor; sometimes a blood sample drawn from a vein in your arm
Test preparation needed?
None
What is being tested?
This test detects characteristic changes (rearrangements) in specific genes in T‑cells. This information can be helpful in diagnosing a T‑cell lymphoma.
T‑cells are a type of lymphocyte (a kind of white blood cell, WBC) that helps to protect the body from infection. Rearrangements in certain parts of their DNA called receptor genes are a normal part of their development. These rearrangements are associated with the development of a large repertoire of diverse T‑cells, allowing them to protect against many different kinds of infections. The final order in which the genes are rearranged is called a gene rearrangement profile. Within any normal population (sample) of T‑cells, the cells and their gene rearrangement profiles are very diverse.
In lymphoma, the T‑cells in affected tissue (such as blood, lymph node, or skin) are identical and their gene rearrangement profiles are likewise identical. Lymphomas arise when an abnormal T‑cell begins to produce numerous identical copies of itself (clones). The cloned cells grow and divide uncontrollably, crowding out normal cells.
A T‑cell receptor gene rearrangement test evaluates the T‑cells in a person’s sample to determine whether the majority of T‑cell rearrangement profiles are diverse or identical. This information, along with clinical signs and symptoms and results of other laboratory tests, can help clarify a person’s diagnosis, or evaluate for persistent or recurrent lymphoma.
B‑cell lymphomas are far more common than T‑cell lymphomas. There are many different types of T‑cell lymphomas, but each is rare.
For additional details about T‑cells and this testing, see Common Questions below.
How is the sample collected for testing?
A bone marrow, lymph node, or other tissue biopsy procedure is performed by a doctor or other trained specialist. Body fluid samples are obtained through collection of the fluid in a container by inserting a needle into the body cavity and aspirating a portion of the fluid with a syringe. Sometimes, a blood sample is obtained by inserting a needle into a vein in the arm.
Is any test preparation needed to ensure the quality of the sample?
No test preparation is needed.
Common questions
T‑cell receptor gene rearrangement testing is used to help diagnose T‑cell lymphomas and to evaluate for residual or recurrent disease after treatment.
Lymphomas arise when an abnormal T‑cell begins to produce numerous identical copies of itself (clones). The cloned cells grow and divide uncontrollably, crowding out normal cells. There are many different types of T‑cell lymphoma and each has different characteristics, prognosis, and a likely response to therapy. Several classification systems have been used to describe them. The most recent is the World Health Organization’s. (For more on this, see the Lymphoma page.)
Testing for T‑cell lymphomas is done in a step-wise fashion and typically starts with:
1. Full Blood Count (FBC) and a WBC differential to evaluate the number, types, and maturity of white blood cells present in the blood. Results may reveal an increased number of lymphocytes and/or presence of abnormal lymphocytes.
2. Analysis of a blood smear, bone marrow, lymph node, skin and/or other tissue biopsy samples is performed. These samples are examined under a microscope, usually by a Histopathologist.
3. If indicated, immunophenotyping is performed on blood, bone marrow, or other tissue (such as an enlarged lymph node or tumour) using a method such as flow cytometry or immunohistochemistry. This test detects the presence or absence of certain markers on the membrane of the cells or inside the cells. These commonly used markers are called clusters of differentiation (CD) and are listed numerically. Patterns of antigens (presence or absence) can provide information as to whether the T‑cells are clones (monoclonal) and can further help classify a T‑cell lymphoma.
A proliferation of T‑cells can be benign or malignant. If, after the above tests are performed, there is still no conclusion as to whether a person has a benign or malignant T‑cell population, a T‑cell receptor gene rearrangement test can be performed.
Testing may sometimes be performed to evaluate the effectiveness of lymphoma treatment – to detect residual or recurrent disease, the continued presence of abnormal monoclonal T‑cells.
Testing is performed when a person has signs and symptoms that suggest a lymphoma, such as:
- One or more swollen but painless lymph nodes—depending on the site of the affected lymph node, symptoms may involve areas of the chest, armpit, neck, abdomen, or groin area, for example.
- Skin lesions
- Enlarged spleen and/or liver
- Fatigue
- Fever
- Night sweats
- Unexplained weight loss
- Neurologic symptoms that may suggest central nervous system involvement
Findings from a FBC and differential may be the first indication that a person might have a lymphoma as symptoms may be absent, mild, or nonspecific.
Testing may be done when other laboratory tests indicate that a lymphoma may be present and/or when other tests are inconclusive. Some examples include:
- An increased number of lymphocytes, especially abnormal-looking lymphocytes, as determined with a FBC and a blood smear examination
- Signs of lymphoma in a tissue biopsy, body fluid or bone marrow sample
- With immunophenotyping (e.g., flow cytometry, immunohistochemistry), antigen groupings that are inconclusive for a T‑cell lymphoma, or when the doctor wants to confirm a diagnosis of lymphoma based on histopathology and immunophenotyping
Testing may also be requested when a person has been treated for a lymphoma to evaluate the effectiveness of treatment and to detect residual or recurrent disease.
Results of testing are typically interpreted by a doctor (Haematologist) who specialises in dealing with blood, blood cells, and bone marrow cells (Hematatology). Results must be interpreted in conjunction with clinical findings, other test results including histopathology, immunophenotyping information, an understanding of the strengths and limitations of different testing methods, and with an understanding of the range of findings that can be found in a “normal” lymphocyte cell population.
This testing helps confirm whether a cloned population of T‑cell lymphocytes is present and helps confirm and/or clarify a person’s diagnosis. In general, if a significant clonal T‑cell population is detected and other associated tests are in agreement, it is likely that the individual tested has a T‑cell lymphoma or that lymphoma has recurred.
Examples of lymphomas that may be detected by this testing include:
- Adult T‑cell leukemia/lymphoma (ATLL)
- Anaplastic large-cell lymphoma
- Angioimmunoblastic T‑cell lymphoma
- Enteropathy-associated T‑cell lymphoma
- Hepatosplenic T‑cell lymphoma
- Mycosis fungoides
- Peripheral T‑cell lymphoma, unspecified
- Precursor T‑cell neoplasm (T lymphoblastic leukemia/lymphoma)
- Sézary syndrome
- T‑cell large granular lymphocytic leukemia
- T‑cell prolymphocytic leukemia
Testing may need to be repeated when the sample does not contain enough DNA to test or if the sample is not suitable for testing.
The detection of a clonal T‑cell receptor gene rearrangement is not synonymous with the presence of T‑cell lymphoma. An individual may have a clonal T‑cell population and not have cancer. Conditions such as autoimmune disorders, certain infections, immune suppression, and immune deficiencies are sometimes associated with small clonal T‑cell populations. This means that one or more groups of cloned T‑cells may be present in a person’s lymphocyte population without it being considered a lymphoma.
If a person is negative for a clonal T‑cell receptor gene rearrangement, the person may still have lymphoma. A test may also be negative if the test method is not sensitive enough to detect the rearrangement or if the clonal lymphocytes from the person tested have mutations that are not detected by the test, or if the lymphoma is of the B‑cell type.
Since false positive and false negative results can be associated with the testing, the results must be interpreted in the context of other clinical and pathological findings.
No. This testing is required only if routine diagnostic procedures are insufficient to make an accurate diagnosis.
No. A positive testing result only helps to confirm a diagnosis of T‑cell lymphoma. The cancer progression and response to treatment is generally determined by the type of a person’s lymphoma, but will also vary from person to person.
This testing requires specialised equipment and interpretation. It is not offered by every laboratory and samples will often need to be sent to a reference laboratory.
During an immune response, it is important that T‑cells be able to distinguish between a person’s own cells and tissues (self) and foreign and/or infected cells (non-self) as the T‑cells are responsible for targeting harmful cells for destruction and for signalling B‑cell lymphocytes (another type of WBC) to begin producing antibodies.
Receptors are protein structures on the surface of T‑cells that allow them to identify and evaluate self and non-self cells and other substances that can produce an immune response (antigens). There are two types of T‑cell receptors, each containing two different subunits. The T‑cell receptor genes control the development of these receptor subunits. Rearrangements in these genes are a normal part of T‑cell development. The purpose of the rearrangements is to produce a wide variety of receptors within the T‑cell population to recognise and address the vast number of antigens that a person may encounter. This means that the receptor gene rearrangements and the receptors in a normal T‑cell lymphocyte population are usually very diverse (polyclonal).
With a T‑cell lymphoma, an abnormal T‑cell lymphocyte begins to clone itself, producing numerous identical cells. The identical, cloned (monoclonal) cells do not function normally, their replication is not regulated, and they may not die as normal cells do. A cancerous monoclonal population of T‑cells accumulates, begins to crowd out normal cells, and may eventually spread throughout the lymphatic system and blood to other lymph nodes and tissue, including the bone marrow.
All of the monoclonal cells produced will have identical T‑cell receptor gene rearrangement profiles. The cancerous (neoplastic) clones are generally large and therefore the clonal cells are the predominant T‑cells present in affected tissue. Detection of a predominant T‑cell receptor gene rearrangement profile often indicates the presence of a neoplastic T‑cell population. This can help to establish the diagnosis of a T‑cell lymphoma or to evaluate for residual or recurrent disease after treatment.