What is a tumor suppressor gene?

A tumor suppressor gene is a type of gene that helps protect the body from cancer. These genes normally control how cells grow, divide, and repair themselves. When working correctly, tumor suppressor genes act like brakes that slow down cell division, fix DNA damage, or cause unhealthy cells to die before they can become cancer. If a tumor suppressor gene becomes damaged or mutated, the brakes can fail to function correctly. This allows cells to grow out of control, potentially leading to the development of cancer.

What do tumor suppressor genes do?

Tumor suppressor genes perform several important functions that keep cells healthy:

• Regulate cell growth – They prevent cells from dividing too quickly or at the wrong time.
• Repair damaged DNA – Some tumor suppressor genes help fix genetic errors that occur during cell division.
• Trigger cell death (apoptosis) – If a cell is too damaged to be repaired, these genes can tell the cell to self-destruct to prevent the damage from spreading.

When a tumor suppressor gene is turned off or lost, these protective functions no longer work, which increases the risk of cancer.

How do tumor suppressor genes contribute to cancer?

For cancer to develop, usually both copies of a tumor suppressor gene must be inactivated or lost. This is called the “two-hit hypothesis.” Everyone inherits two copies of most genes—one from each parent. If both copies of a tumor suppressor gene are damaged, cells lose control over their growth.

Some people are born with one damaged copy of a tumor suppressor gene, which increases their risk of developing certain types of cancer. These inherited changes are referred to as germline mutations and can be passed down through family members. Additional damage to the second copy during a person’s lifetime may lead to cancer.

What are examples of tumor suppressor genes?

Several well-known tumor suppressor genes are linked to specific types of cancer.

Examples include:

• TP53 – One of the most important tumor suppressor genes. It helps prevent cells with damaged DNA from growing. Mutations in TP53 are found in many different types of cancer.
• RB1 – Associated with retinoblastoma, a rare eye cancer in children. It also plays a role in other types of cancer.
• BRCA1 and BRCA2 – Tumor suppressor genes involved in breast and ovarian cancer. Inherited mutations in these genes significantly increase the risk of cancer.
• APC – A gene that helps prevent the formation of colon polyps and colorectal cancer.
• PTEN – Involved in cell growth and regulation. Mutations can lead to cancers of the breast, thyroid, and other organs.

How are tumor suppressor genes tested?

Tumor suppressor genes are most often tested using a method called next-generation sequencing (NGS). This is a powerful technology that allows scientists to read the genetic code (DNA) in a tissue or blood sample. NGS can look at many genes at once, including tumor suppressor genes, to identify any mutations (changes) that may be important for diagnosing or treating cancer.

NGS testing can be done in two main ways:

• Germline testing – This is done on a blood or saliva sample to look for inherited mutations in tumor suppressor genes (such as BRCA1, BRCA2, or TP53). Germline mutations are present from birth and can be passed down in families.
• Somatic testing (tumour profiling) – This is done on a tumour tissue sample, usually after a biopsy or surgery, to look for mutations that developed in the tumour cells. These are not inherited and are found only in the tumour.

What do the results show?

NGS results may report different types of changes in tumor suppressor genes, including:

• Pathogenic mutations – These are changes known to cause disease or increase the risk of cancer.
• Likely pathogenic mutations – These are changes that are likely to be harmful but require further evidence.
• Variants of uncertain significance (VUS) – These are changes where it is not yet known if they are harmful or harmless.
• Benign or likely benign variants – These are harmless changes that do not affect gene function.

The report may also include information about whether both copies of the gene are affected and whether the change is inherited or only found in the tumour.

NGS can also examine other important genes and features of the tumor, such as DNA repair defects, microsatellite instability (MSI), or tumor mutational burden (TMB), all of which may inform treatment choices.

Your doctor or a genetic counselor will help explain what the results mean for you and whether your family members should also be tested.

Why is this information important?

Knowing whether a tumour suppressor gene is mutated can help:

• Explain why a cancer developed.
• Determine cancer risk for other family members.
• Guide treatment decisions, especially when certain mutations affect how a tumour responds to therapy.
• Inform screening strategies to detect cancer early in people with inherited mutations.

Questions to ask your doctor

• Was a tumor suppressor gene mutation found in my tumour or genetic test?
• Is this mutation inherited or only present in the tumour?
• Do I need genetic counseling or additional testing?
• How does this finding affect my treatment or cancer risk?