Acquired vs. Inherited Mutations in Cancer: What You Need to Know 

A gene mutation is a change in the genetic instructions in a cell. Genes are the DNA-encoded instructions for building proteins, which are the machinery that does the work inside our cells and our bodies. Some mutations change the function of proteins in ways that increase the risk of cancer or drive its growth.  

Gene mutations are not all the same. An understanding of the difference between acquired mutations and inherited mutations can help you make better decisions about cancer care and prevention. 

What is the difference between an acquired and an inherited mutation? 

An acquired mutation is acquired during your lifetime. You are not born with the mutation and there is little risk of passing it on to your children. 

“Age is the biggest risk factor for acquired mutations,” says Anu Chittenden, MS, CGC, a certified genetic counselor at Dana-Farber. “The longer we live, the more likely we are to acquire these mutations that happen by chance.” 

In contrast, an inherited mutation is passed down from one or both parents. The mutation is present in the DNA in the egg or sperm at the time of conception and exists in every cell of your body.  

How do mutations occur? 

Acquired mutations, also called somatic mutations, can occur due to stressors that cause damage. For example, if you get a sunburn and the UV radiation damages the DNA in a cell, you have acquired a mutation. Damaged cells often die, but if the cell survives it can pass that mistake on to other cells when it copies its DNA during cell division. 

Acquired mutations can also occur as cells divide. Cells copy their DNA instructions letter-by-letter and can make mistakes, such as deleting, adding, or switching a letter. The body has its own proofreading systems to help prevent or correct these mistakes, but they are not perfect. Not all mistakes result in the creation of genes that don’t work properly, but over time, mutations can accumulate in ways that affect health. 

Inherited mutations occur in the cells that become egg or sperm cells. Cells can make random errors as they copy the genetic code, and those errors end up in an egg or a sperm cell and are copied over and over as your body develops.  

These mutations, called germline mutations, can have no effect, be detrimental to health, or be beneficial, or sometimes have both positive and negative effects. For example, the gene mutation responsible for sickle cell anemia occurred between 7,000 to 22,000 years ago in the tropics. People with the mutation were protected from malaria. But when both parents have this mutation and pass it along to a child, the error results in malformed red blood cells and causes sickle cell disease. 

How can you find out if you have a mutation related to cancer? 

Tumor genomic testing identifies acquired mutations. If you have an acquired mutation, you won’t know about it until it causes a problem. If you develop cancer, your oncologist might suggest tumor genomic testing.  

This is a test of the cells taken from a biopsy of the tumor. It looks for specific acquired gene mutations known to drive the cancer. Tumor genomic tests can sometimes point your doctor to precision medicine that is designed to treat cancer by addressing problems that occur because of a specific acquired mutation. Sometimes, tumor genomic testing can find inherited mutations too. 

Germline genetic testing identifies inherited mutations. Inherited mutations also tend to be silent until you see a clue, such as a pattern of cancer in your family. If you suspect that you have an inherited mutation, a genetic counselor might suggest germline genetic testing.  

This is a test of normal cells in your body taken from saliva or blood. It looks for mutations in specific genes that are known to run in families and increase the risk of cancer. Germline testing can sometimes point your doctor to preventive measures that can reduce your risk of cancer or to precision medicine to treat cancer. Germline genetic testing through medical-grade laboratory tests differs from recreational genetic testing because the tests are designed to be more accurate. 

Do acquired and inherited mutations cause cancer? 

One or two acquired mutations probably won’t lead to cancer. But over time, if you accumulate more and more mutations, a cascade of changes could occur that could eventually lead to cancer.  

Inherited mutations that are associated with cancer don’t directly cause cancer, but they do increase the risk that cancer will develop at some point in a person’s lifetime.  

An example of an inherited risk of cancer is Lynch syndrome. A person with Lynch syndrome has an elevated risk of colorectal, endometrial, stomach, ovarian, urinary tract, other intestinal cancers, and additional cancers.

The increased risk is due to a mutation in one of several genes that fix mistakes made when DNA is copied. These genes are called DNA mismatch repair genes. The body has many mechanisms that work hard to prevent DNA copying errors and protect against cancer. When one of those mechanisms is disabled by mutations, cancer is more likely to occur and at a younger age.

Almost all cells in the body have two inherited copies of each of these DNA mismatch repair genes. One copy comes from the mother and the other from the father. A person with Lynch syndrome has inherited one mutated copy of the gene, so they still have one normal copy of the gene that continues to function and protect against errors.

If that person acquires a mutation in the second copy of that gene, the damaged mechanism to repair DNA errors will not work correctly. In this case, the person becomes very likely to develop cancer. Visit Dana-Farber’s Lynch Syndrome Center for more information about diagnostics and treatment for the disease.

In rare cases, both parents pass along a mutation in the same DNA mismatch repair gene. In this case, that repair mechanism is damaged from birth. A person with this condition, called constitutional mismatch repair deficiency syndrome, has a very high risk of cancer, and could even develop multiple forms of cancer during childhood.

Where can I get more information? 

If you are concerned about an inherited risk of cancer, speak to your doctor about setting up an appointment with a genetic counselor. A genetic counselor, such as those in Cancer Genetics and Prevention at Dana-Farber Cancer Institute, can help you decide if germline genetic testing is right for you.  

If you are being treated for cancer, speak to your oncologist about tumor genomic testing. Your oncologist can let you know of tumor genomic testing might provide insights about your cancer that will help guide treatment choices. They may also recommend germline genetic testing.