Why are Tumor Suppressor Genes Important in Cancer?

Tumor Suppressor Genes - Function, Abnormalities, and Role in Cancer

strand of DNA with colored base pairs representing a mutation
What are tumor suppressor genes?. istockphoto.com

What are tumor suppressor genes? How are these different than oncogenes, and what role do they play in the development of cancer and hereditary cancer?

Definition: Tumor Suppressor Genes

Tumor suppressor genes are genes that regulate the growth of cells. When these genes are functioning properly, they can prevent and inhibit the growth of tumors.

When tumor suppressor genes are altered or inactivated (due to a mutation), they lose the ability to make a protein that controls cell growth. Cells can then grow uncontrolled and develop into a cancer.

Types of Tumor Suppressor Genes

There are 3 main types of tumor suppressor genes.

  • One type tells cells to slow down and stop dividing.
  • Another type is responsible for fixing damages in DNA that can happen when cells divide (DNA repair genes.)
  • A third type is responsible for telling cells when to die, a process called apoptosis or programmed cell death.

Analogy to Driving - Tumor Suppressor Genes are the Brakes

With all the news about immunotherapy, and hearing bits and pieces about "on and off switches" it cancer, it may help to, very simplistically, think of cells as a car.  In each cell, there is an accelerator and brakes. In normal cars, both are working fine. Multiple processes make sure they stay in balance so the car both moves along regularly, but doesn't crash.

Cancer begins with a series of mutations. Some mutations are no big deal—we refer to them as passenger mutations. The problem mistakes are those that involve the driver. The driver can decide to go too fast or slow. You may hear about these as "driver mutations" not because they drive a car, but because they drive the growth of cancer cells.

Cancer can be related to problems with either the accelerator or the brakes, but usually, damage to genes controlling both of these is needed to cause a cancer. The fact that cancer often requires a number of different mutations is one of the reasons why cancer is more common in older people.

Oncogenes are, in analogy, genes that control the accelerator.  The term oncogenes means literally "cancer genes."

Tumor suppressor genes, in contrast to oncogenes, are the brakes. Tumor suppressor genes act like a blueprint. They code for proteins which are then responsible for going out and hitting the brakes.

Most of the time for a cell to become cancer, it requires mutations in both oncogenes and tumor suppressor genes. In other words, the accelerator has to be stuck to the floor AND the brakes have to malfunction.  

Oncogenes vs Tumor Suppressor Genes

There are several important differences between oncogenes and tumor suppressor genes in cancer. In general, oncogenes are dominant. In our bodies, we have two sets of each of our chromosomes and two sets of genes - one from each of our parents. Often if one gene isn't working well, the other can compensate. You may have heard of inheritance. If you have heard about the inheritance of eye color, the difference between most oncogenes and tumor suppressor genes is easier to understand. Oncogenes tend to be dominant—such as brown eyes. If either of the genes may push the accelerator too hard, it can contribute to cancer. Tumor suppressor genes, in contrast, tend to be recessive. That is, just like you need two genes for blue eyes to have a blue eyed baby, two suppressor genes must both be damaged in order to contribute to cancer.

Tumor Suppressor Genes and Recessive Inheritance - The "2 Hit Hypothesis"

Understanding the recessive nature of tumor suppressor genes can be helpful in understanding genetic predispositions to a disease.

An example is the tumor suppressor genes BRCA1/BRCA2 - otherwise known as the "breast cancer genes." People who have a mutation in one of these genes have an increased risk of developing breast cancer (among others.) But not everyone with the gene develops breast cancer. When the second non-mutated gene becomes mutated, an acquired mutation, meaning a somatic mutation that occurs after birth, cancer may result.

This recessive nature is what is referred to if you hear of the "2 hit hypothesis" of cancer. Some cancers begin (at least on the tumor suppressor end, but keep in mind that there is also usually an oncogene mutation as well) after 2 mutations in a tumor suppressor gene. The first mutation may be present from birth, known as "germ mutation." The second, a "somatic mutation" is acquired and related to something in the environment after birth.


Tumor suppressor genes were first identified among children with retinoblastoma. In retinoblastoma, in contrast, the tumor suppressor gene that is inherited is dominant—and therefore allow cancers to develop in young children.

Tumor Suppressor Genes

There have now been several tumor suppressor genes identified.  Some of these include:

  • RB - The suppressor gene responsible for retinoblastoma
  • p53 gene - The p53 gene codes for a protein p53.which regulates gene repair in cells.  Mutations in this gene are implicated in around 50 percent of cancers.
  • B RCA1/BRCA2 - These genes are responsible for around 5 percent to 10 percent of breast cancers. (BRCA2 is also linked to an increased lung cancer risk in women.)
  • APC gene - These genes are associated with an increased risk of colon cancer in people with familial adenomatous polyposis.

Why Cancer Treatments Do Not Always Work

Understanding tumor suppressor genes may also help explain a bit why therapies, such as chemotherapy, don't completely cure cancer. Some cancer treatments work to stimulate cells to commit suicide. Since some tumor suppressor genes are involved in the process of apoptosis (cell death) the cancer cells may not go through the process of apoptosis as other cells might.

More About Cancer

Learning about tumor suppressor genes is just one part of understanding the development and survival of cancer. Learn about exactly what is a cancer cell, and how cancer cells differ from normal cells.

Also Known As: antioncogene, loss of function genes

Examples: Many lung cancers have abnormal p53 genes within the tumor. p53 is a tumor suppressor gene that is responsible for making sure cells die if their DNA is damaged and cannot be repaired (apoptosis).

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