- Oncogenes, Tumor Suppressor Genes, and Cancer
- How do cells know what to do?
- What are mutations?
- Gene mutations that can lead to cancer
- How can oncogenes and tumor suppressor genes be used to help prevent cancer?
- How can oncogenes and tumor suppressor genes be used to help guide treatment of cancer?
Gene mutations that can lead to cancer
The 2 main types of genes that play a role in cancer are oncogenes and tumor suppressor genes.
Most oncogenes are mutations of certain normal genes called proto-oncogenes. Proto-oncogenes are the "good" genes that normally control what kind of cell it is and how often it divides. When a proto-oncogene mutates (changes) into an oncogene, 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.
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.
As scientists learn more about oncogenes, they may be able to develop drugs that inhibit or stop them. Some drugs that target oncogenes are already being used, and more are on the way. This is discussed in more detail later on in this document.
Inherited mutations of oncogenes
A few cancer syndromes are caused by inherited mutations of proto-oncogenes that cause the oncogene to be turned on (activated). For example, multiple endocrine neoplasia type 2 (MEN2) is caused by an inherited mutation in the gene called RET. People affected by this syndrome often develop an uncommon thyroid cancer called medullary cancer of the thyroid. They also develop other tumors, including pheochromocytoma and nerve tumors. Inherited mutations in the gene called KIT can cause hereditary gastrointestinal stromal tumors (GISTs). And inherited mutations in the gene called MET can cause hereditary papillary renal cancer.
Acquired mutations of oncogenes
Most cancer-causing mutations involving oncogenes are acquired, not inherited. They generally activate oncogenes by chromosome rearrangements, gene duplication, or mutation. For example, a chromosome rearrangement can lead to formation of the gene called BCR-ABL, which leads to chronic myeloid leukemia (CML). Acquired mutations that activate the KIT gene cause most cases of gastrointestinal stromal tumor (GIST).
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. Many different tumor suppressor genes have been found, including TP53 (p53), BRCA1, BRCA2, APC, and RB1.
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 mutations of tumor suppressor genes
Inherited abnormalities of tumor suppressor genes have been found in some family cancer syndromes. They cause certain types of cancer to run in families. For example, a defective APC gene causes familial adenomatous polyposis (FAP), a condition in which people develop hundreds or even thousands of colon polyps. Often, at least one of the polyps becomes cancer, leading to colon cancer. There are many examples of inherited tumor suppressor gene mutations, and more are being discovered each year. For more information about inherited mutations and cancer, see our document Heredity and Cancer.
Acquired mutations of tumor suppressor genes
Tumor suppressor gene mutations have been found in many cancers. Most of these 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, including lung, colorectal, and breast cancer. The p53 protein is involved in the pathway to apoptosis. This pathway is turned on when a cell has DNA damage that can't be repaired. If the gene for p53 is not working properly, cells with damaged DNA continue to grow and divide. Over time this can lead to cancer.
Acquired changes in many other tumor suppressor genes also contribute to the development of sporadic (not inherited) cancers.
Last Medical Review: 12/27/2011
Last Revised: 12/27/2011