Oncogenes and Tumor Suppressor Genes

Two of the main types of genes that play a role in cancer are oncogenes and tumor suppressor genes.

Oncogenes

Proto-oncogenes are genes that normally help cells grow. When a proto-oncogene mutates (changes) or there are too many copies of it, it becomes a “bad” gene that can become permanently turned on or activated when it is not supposed to be. When this happens, the cell grows out of control, which can lead to cancer. This bad gene is called an oncogene.

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

A few cancer syndromes are caused by inherited mutations of proto-oncogenes that cause the oncogene to be turned on (activated). But most cancer-causing mutations involving oncogenes are acquired, not inherited. They generally activate oncogenes by:

• Chromosome rearrangements: Changes in chromosomes that put one gene next to another, which allows one gene to activate the other
• Gene duplication: Having extra copies of a gene, which can lead to it making too much of a certain protein

Tumor suppressor genes

Tumor suppressor genes are normal genes that slow down cell division, repair DNA mistakes, or tell cells when to die (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 keeps the cell from dividing too quickly, just as a brake keeps a car from going too fast. When something goes wrong with the gene, such as a mutation, cell division can get out of control.

An important difference between oncogenes and tumor suppressor genes is that oncogenes result from the activation (turning on) of proto-oncogenes, but tumor suppressor genes cause cancer when they are inactivated (turned off).

Inherited abnormalities of 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, not inherited.

For example, abnormalities of the TP53 gene (which codes for the p53 protein) have been found in more than half of human cancers. Acquired mutations of this gene appear in a wide range of cancers.