Tumor Suppressor Gene: Definition

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A tumor suppressor gene helps protect the body from cancer. It works like a brake on cell growth. When both copies stop working, cells can grow out of control and form a tumor.

This article explains what tumor suppressor genes do, how losing them leads to cancer, how pathologists test for them, and what your report may say.

What is a tumor suppressor gene?

A tumor suppressor gene keeps cell growth in check. Its protein slows cell division, repairs damaged DNA, or tells badly damaged cells to die. Doctors often compare these genes to a car’s brakes.

Oncogenes work the other way. An oncogene pushes cells to grow, like an accelerator. Cancer often develops when the brakes fail, and the accelerator gets stuck.

What do tumor suppressor genes do?

Tumor suppressor genes protect cells in three main ways:

Controlling cell division. They stop cells from dividing too often or at the wrong time.
Repairing DNA. Some fix DNA errors before the cell divides.
Removing damaged cells. Some tell a badly damaged cell to die. Doctors call this programmed cell death, or apoptosis.

How does losing a tumor suppressor gene lead to cancer?

Each cell has two copies of most genes, one from each parent. For most tumor suppressor genes, one working copy is enough to keep the brake on. Cancer can develop when both copies stop working. Doctors call this a “two-hit” process.

A gene copy can stop working in several ways:

A mutation. A mutation changes the DNA code so the protein no longer works.
A deletion. Part or all of the gene goes missing.
Silencing. A chemical tag switches the gene off without changing its code. For example, MLH1 promoter methylation turns off a DNA repair gene.

Can you inherit a tumor suppressor gene change?

Most tumor suppressor gene changes in cancer are not inherited. They develop only in the tumor cells during a person’s life. Doctors call these somatic mutations. They cannot be passed to children.

Some people are born with one damaged copy in every cell. This is a germline change. These people need only one more hit to lose the gene, so their cancer risk is higher. They can pass the change to their children. Doctors call this a hereditary cancer syndrome. Examples include:

Hereditary breast and ovarian cancer. Linked to BRCA1 and BRCA2.
Lynch syndrome. Linked to the mismatch repair genes.
Li-Fraumeni syndrome. Linked to TP53.
Familial adenomatous polyposis. Linked to APC.
Von Hippel-Lindau syndrome. Linked to VHL.
Hereditary retinoblastoma. Linked to RB1. It raises the risk of retinoblastoma, often in both eyes, and of osteosarcoma.

What are some common tumor suppressor genes?

Pathologists and doctors test for many tumor suppressor genes. Some of the best known are:

TP53. This gene makes the p53 protein, which stops damaged cells from dividing. TP53 changes occur in many cancers.
RB1. This gene controls when cells divide. Almost all retinoblastomas, a rare childhood eye cancer, come from loss of both copies.
BRCA1 and BRCA2. These genes repair damaged DNA. See BRCA1 and BRCA2.
Mismatch repair genes. MLH1, PMS2, MSH2, and MSH6 fix DNA copying errors. See mismatch repair.
PTEN. This gene helps control cell growth. See PTEN.

How do pathologists test for tumor suppressor genes?

Pathologists use two main kinds of tests:

Immunohistochemistry. This stain shows whether tumor cells still make the protein. When a gene is lost, the protein often disappears from the tumor cells, while nearby normal cells still stain. For p53, a very strong stain can also point to a mutation. See immunohistochemistry.
Genetic testing. Next-generation sequencing reads the DNA directly. Testing on tumor tissue finds changes in the tumor. Testing on blood or saliva finds changes present from birth.

What might my report say about a tumor suppressor gene?

Reports describe tumor suppressor gene results in a few standard ways. Each laboratory phrases them a little differently:

Retained or lost. On immunohistochemistry, retained means the tumor still makes the protein. Lost means it does not.
Normal or abnormal (aberrant) pattern. For p53, the report may describe a wild-type pattern or an abnormal pattern that suggests a mutation.
Pathogenic or likely pathogenic variant. Genetic testing found a change known or likely to damage the gene.
Variant of uncertain significance. Genetic testing found a change whose effect is not yet known. See variants of uncertain significance.
Germline or somatic. The report may state whether you inherited the change or whether it is only in the tumor.

Questions to ask your doctor

Was a tumor suppressor gene change found in my tumor?
Was the change found by immunohistochemistry, genetic testing, or both?
Is the change inherited, or is it only in the tumor?
Should I see a genetic counselor?
Should my family members have testing?
Does this change affect my treatment options?
Does this change affect my risk of other cancers?