Gene Mutations

For Patients & Parents

Since there are many possible combinations of the DNA chemicals A, G, C, and T, there are many different genes. The order of As, Gs, Cs, and Ts is important because this order tells cells how to work and what to make. A cell’s job includes making proteins. Proteins are substances that build bones, allow your muscles to move, control your digestion, and keep your heart beating.

Changes in the order of As, Gs, Cs, and Ts happen regularly and naturally. These changes are called mutations, and they affect cells in many different ways. For example, some mutations (gene changes) stop the gene from making a certain protein. Other mutations change how the protein is made, so it no longer works. Some mutations make a gene too active, so it makes more protein than usual. Some do not cause any health problems, but others cause diseases like cancer.

You can inherit a gene mutation from your parents or it can happen during your lifetime. Usually, mutations do not change the way a gene works very much. A cell can usually fix any damage using other genes that repair DNA. Once it is fixed, the gene can do its normal activities again.

When a mutation cannot be fixed, it can change the way a gene works. This can cause health problems. For example, in sickle cell disease, a mutation that changes the shape of red blood cells makes it difficult for the blood to carry oxygen to your organs. Patients with this disease have pain and other health problems caused by the mutation. DNA mutations can also cause tumors. While many different genes and mutations cause tumors, a mutation in the TP53 gene is one of the most common. Almost all adrenocortical tumors (ACT) in children are linked to having a TP53 mutation.

Here is one way to think about mutations. When you see the word CAT written in English, you probably think of a small, furry animal that purrs and might be a pet in your home. In a sentence, this word should make sense. For example, if you read, “The dog chases the cat,” you know what it means. But if you switch the T and the C in CAT, the new word is TAC. The sentence says, “The dog chases the tac,” and you do not know what it means. In the same way, when the As, Gs, Cs, and Ts in your genes are not in the right order, your cells cannot read the messages from your genes. Your body can get confused and stop working properly. A change in just 1 (one) of the As, Gs, Cs, and Ts can have a major effect.

Scientists do not always know what causes a mutation. Some are caused by things outside your body (environmental causes). They include:

  • Radiation,
  • Long-term exposure to hazardous chemicals, and
  • Virus exposure.

Other mutations happen when cells divide to make new cells. These mutations are mistakes your body makes (somatic mutations). Some mutations are inherited (passed down) from your parents. These are called germline mutations.

Sometimes mutations occur only in an egg cell or sperm cell, or just after the egg is fertilized by the sperm cell. These are called de novo mutations (new mutations). Someone with a de novo mutation is the first member of the family to have the condition caused by the mutation.

All germline (inherited) mutations started as de novo mutations in a family member.

No matter where a mutation comes from, it can take many years for it to cause a tumor. This is why most people who have cancer get it in their 40s, 50s, or even later. However, scientists know that people with germline (inherited) mutations can get cancers much younger, including during childhood.

drawing of somatic and germline mutations
Drawing of de novo mutations