Oncogenes, Tumor Suppressor Genes, and DNA Repair Genes

Our bodies are made up of trillions of cells, which must work together to keep us healthy. Our cells need to be able to divide to make new cells to help the body grow, or to replace cells that have died. At the same time, cell growth and division need to be controlled, so the cells don’t grow too much and crowd out the cells around them.

It may be helpful to think of a cell as a car. For it to work properly, there need to be ways to control how fast it goes – that is, ways to speed up cell growth and division if it’s needed (like a gas pedal), and ways to keep this growth under control or slow it down (like a brake pedal). There also need to be ways to fix parts of the car if they break down.

Cell growth is normally controlled by the actions of certain genes inside each cell. Cancer begins when cells in the body become abnormal and start to grow out of control. This happens where there are changes in genes that affect cell growth.

The main types of genes that play a role in cancer are:

• Oncogenes
• Tumor suppressor genes
• DNA repair genes

Cancer is often the result of changes in more than one of these types of genes within a cell.

Oncogenes

Proto-oncogenes are genes that normally help cells grow and divide to make new cells, or to help cells stay alive. When a proto-oncogene mutates (changes) or there are too many copies of it, it can become turned on (activated) when it is not supposed to be, at which point it's now called an oncogene. When this happens, the cell can start to grow out of control, which might lead to cancer.

A proto-oncogene normally functions in a way much like the gas pedal on a car. It helps the cell grow and divide. An oncogene is like a gas pedal that is stuck down, which causes the cell to divide out of control.

Oncogenes can be turned on (activated) in cells in different ways. For example:

• Gene variants/mutations: Some people have differences in the ‘code’ of their genes that can cause an oncogene to be turned on all the time. These types of gene changes can be inherited from a parent, or they can occur during a person’s life, when a mistake is made when copying the gene during cell division.
• Epigenetic changes: Cells normally have ways of turning genes on or off that don’t involve changes in the genes themselves. Instead, different chemical groups can be attached to genetic material (DNA or RNA) that affect whether a gene is turned on. These types of epigenetic changes can sometimes lead to an oncogene being turned on. For more on epigenetic changes, see Gene Changes and Cancer.
• Chromosome rearrangements: Chromosomes are long strands of DNA in each cell that contain its genes. Sometimes when a cell is dividing, the sequence of the DNA in a chromosome can be changed. This might put a gene that functions as a type of ‘on’ switch next to a proto-oncogene, keeping this gene turned on even when it shouldn’t be. This new oncogene can result in the cell growing out of control.
• Gene duplication: Some cells have extra copies of a gene, which might lead to them making too much of a certain protein.

A small number of family cancer syndromes are linked to an inherited change in an oncogene. These types of changes can sometimes be the first step in a cell becoming a cancer cell. But most changes involving oncogenes are acquired during a person’s lifetime, rather than being inherited. 

Tumor suppressor genes

Tumor suppressor genes are normal genes that slow down cell division or tell cells to die at the right time (a process known as apoptosis or programmed cell death). When tumor suppressor genes don't work properly, cells can grow out of control, which can lead to cancer.

A tumor suppressor gene is like the brake pedal on a car. It normally helps keep the cell from dividing too quickly, just as a brake keeps a car from going too fast. When something goes wrong with a tumor suppressor gene, such as a pathogenic variant (mutation) that stops it from working, cell division can get out of control.

Inherited changes in tumor suppressor genes have been found in some family cancer syndromes. They cause certain types of cancer to run in families. But most tumor suppressor gene mutations are acquired during a person's lifetime, not inherited.

For example, TP53 is an important tumor suppressor gene. It codes for the p53 protein, which helps keep cell division under control. Inherited changes in the TP53 gene can lead to Li-Fraumeni syndrome. Family members with this syndrome have an increased risk of several types of cancer, because all of their cells have this TP53 gene change. 

Changes in the TP53 gene are also very common in cancer cells in people without an inherited cancer syndrome. These TP53 changes are acquired during the person’s life. These changes can help the cancer cells grow, but they are found only in the cancer cells, not in other cells in the body, so they can’t be passed on to a person’s children.

DNA repair genes

When a cell divides to make new cells, it needs to make a new copy of all of its DNA. This is a complex process, and sometimes it results in mistakes in the DNA.

Genes known as DNA repair genes act like a person who repairs a car. They help fix mistakes in the DNA, or if they can’t fix them, they trigger the cell to die so the mistakes can’t cause any further problems. 

When something goes wrong with one of these DNA repair genes, it can allow more mistakes to build up inside the cell. Some of these might affect other genes, which could lead to the cell growing out of control.

As with other types of gene changes, changes in DNA repair genes can either be inherited from a parent or acquired during a person’s lifetime.

Examples of DNA repair genes include the BRCA1 and BRCA2 genes. People who inherit a pathogenic variant (mutation) in one of these genes have a higher risk of some types of cancer, particularly breast and ovarian cancer among women. (For more information, see Family Cancer Syndromes.) But changes in these genes are also sometimes seen in tumor cells in people who did not inherit one of these mutations.