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Burkitt Lymphoma Genetic Causes

Medically reviewed by Mark Levin, M.D.
Written by Maureen McNulty
Posted on August 5, 2021

Burkitt lymphoma, a fast-growing cancer, is a type of non-Hodgkin lymphoma (NHL). Burkitt lymphoma cells contain many genetic changes that cause them to act differently than normal cells.

There are three types of Burkitt lymphoma:

  • Endemic Burkitt lymphoma most often develops in children living in Africa.
  • Sporadic Burkitt lymphoma affects children worldwide and is very rare in adults.
  • Immunodeficiency-related Burkitt lymphoma usually develops in people who have immune system problems. This includes people who have had an organ transplant and need to take immunosuppressive drugs and those with immune system disorders such as AIDS.

What Causes Burkitt Lymphoma?

All types of cancer, including Burkitt lymphoma, are caused by gene changes (mutations). Each gene acts as a set of instructions that tells a cell how to make a particular protein. Proteins go on to perform different tasks within the cell. Through this process, genes control how a cell acts, tell it when to grow and divide, and determine how long the cell will live.

Mutations can disrupt how a cell normally works. Gene changes may make cells grow too quickly, prevent cells from dying when they should, or stop cells from fixing the damage. If too many gene changes build up within a cell, it may become cancerous.

Lymphoma develops in lymphocytes — white blood cells that help the body fight infection. Burkitt lymphoma develops from a type of lymphocyte called a B cell. When B cells develop certain gene changes, they can turn into lymphoma cells and start to grow out of control.

Burkitt Lymphoma Is Not Inherited

People develop gene changes in two main ways. In some cases, gene changes are inherited from parents. Inherited changes are found in every cell in the body and are present at birth. Other gene changes are acquired. They occur in a single cell throughout a person’s life. Acquired gene changes may be caused by things in the environment that damage cells, such as UV light or tobacco smoke. They may also develop when a cell makes a mistake as it divides.

Burkitt lymphoma is almost always caused by acquired gene changes. Researchers have only reported one case in which Burkitt lymphoma occurred in two people within the same family. Almost everyone with Burkitt lymphoma has no family history of the disease. This means that a parent with Burkitt lymphoma won’t pass the disease on to their child.

Although Burkitt lymphoma is not inherited, it is linked to other conditions that are. Some people inherit immune deficiency disorders. These are genetic disorders in which the immune system has trouble fighting infections. People with these conditions are more likely to develop immunodeficiency-related Burkitt lymphoma. Inherited disorders that may increase a person’s chances of Burkitt lymphoma include ataxia-telangiectasia, Wiskott-Aldrich syndrome, and X-linked lymphoproliferative syndrome type 1.

Gene Changes in Burkitt Lymphoma

Identifying gene abnormalities within cancer cells can help with diagnosis. People with lymphoma may undergo cytogenetic or sequencing tests to figure out which type of lymphoma they have. Learning more about the genetics of Burkitt lymphoma may also help researchers understand how to treat this condition more effectively. For example, if researchers find that tumor cells have changes in a particular gene, they may be able to treat cancer with drugs that block that gene.

C-MYC

About 95 percent of people with Burkitt lymphoma have an acquired gene change called a chromosome translocation. Chromosomes are long pieces of DNA that contain a cell’s genes. When a chromosome becomes damaged, it may break. Part of one chromosome may abnormally attach to part of a different chromosome. This is known as a translocation.

Most people with Burkitt lymphoma have a chromosomal translocation in their lymphocytes. This translocation affects c-MYC, an important gene that helps cells grow.

Usually, the c-MYC gene is only turned on during cell proliferation (the process in which a cell divides and makes more copies of itself). In people with Burkitt lymphoma, the chromosome translocation causes c-MYC to move to a different chromosome, next to a gene called immunoglobulin heavy chain (IgH). Lymphocytes frequently need to turn on this immunoglobulin gene to make antibodies (infection-fighting proteins). When IgH and c-MYC are located beside one another, as is the case in Burkitt lymphoma cells, the cells accidentally turn on c-MYC. Too much c-MYC makes the cells divide faster than they should.

Other Genes

Researchers have also found other acquired gene changes in Burkitt lymphoma cells. About 1 out of 3 people with Burkitt lymphoma have mutations in a gene called ID3. Researchers believe that ID3 gene mutations also make cells grow and divide.

People with Burkitt lymphoma may also have other gene mutations. Some people have mutations in genes like ARID1A, SMARCA4, and TP53. These genes are tumor suppressors — they normally stop cells from growing out of control. When tumor suppressors are mutated, they don’t work properly to stop a cell from becoming cancerous. The genes PIK3R1 and NOTCH1 are also frequently mutated in people with Burkitt lymphoma. These genes are oncogenes — they encourage cells to grow too quickly.

Burkitt Lymphoma and Infection

People with a history of certain infections are more likely to develop the different subtypes of Burkitt lymphoma. People who have been infected with the Epstein-Barr virus (EBV) or malaria develop endemic Burkitt lymphoma at higher rates. The Epstein-Barr virus can also increase a person’s chances of developing sporadic Burkitt lymphoma and is associated with the childhood African variant of Burkitt lymphoma. Immunodeficiency-associated Burkitt lymphoma is more likely to develop in people with HIV, the virus that leads to AIDS.

Researchers don’t know why Burkitt lymphoma is linked to certain infections. However, they think that infection may sometimes lead to cancer-causing gene changes. For example, both EBV and the parasite that causes malaria may turn on genes that help damaged cells avoid death. The malaria parasite also turns on the toll-like receptor 9 gene, which helps create the MYC translocations that cause Burkitt lymphoma.

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Are you living with Burkitt lymphoma? Share your experiences in the comments below, or start a conversation by posting on your Activities page.

Posted on August 5, 2021
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Mark Levin, M.D. is a hematology and oncology specialist with over 37 years of experience in internal medicine. Review provided by VeriMed Healthcare Network. Learn more about him here
Maureen McNulty studied molecular genetics and English at Ohio State University. Learn more about her here

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