TP53 Gene Mutations (Li-Fraumeni Syndrome)

What is TP53 and Li-Fraumeni syndrome?

TP53 is a gene that helps repair damage to your DNA. People who are born with changes—called mutations—in the TP53 gene have a syndrome known as Li-Fraumeni syndrome and an increased risk for many different types of cancer.   

Does everyone with Li-Fraumeni syndrome develop cancer?

The lifetime risk for cancer with a TP53 mutation is very high, and most people with an inherited mutation in the TP53 gene will develop cancer in their lifetime. Following the guidelines for screening and prevention increases the chances of preventing cancer or catching it at its earliest and most treatable stage.

My tumor has a TP53 mutation. Does that mean I have Li-Fraumeni syndrome?

No, testing positive for a TP53 mutation in your tumor does not necessarily mean you have Li-Fraumeni syndrome. 

TP53 mutations in tumors

Tumor testing (also known as biomarker testing) can look for different mutations within a cancer cell. Doctors order these tumor tests to make decisions about the best way to treat the cancer. Unlike normal cells, cancer cells often have many different types of mutations. Mutations that are only found within cancer cells are called acquired (somatic) mutations. TP 53 is a common somatic mutation found in cancer cells. People with somatic TP53 mutations in their cancer cells do not develop Li-Fraumeni syndrome.  

Germline TP53 mutations

Most people who are born with TP53 mutations inherited the mutation from one of their parents. These people will have the mutation in every cell in their body. Mutations that are  inherited are called germline mutations. People with germline TP53 mutations have Li-Fraumeni syndrome. Genetic testing is used to test people for an inherited mutation in TP53 and Li-Fraumeni syndrome. 

De Novo TP53 mutations

Some people with Li-Fraumeni syndrome did not inherit their TP53 mutation from either parent. This is known as a de novo mutation. De novo mutations happen to a person during development in the womb before they are born. People with de novo TP53 mutations may develop Li-Fraumeni cancers, but depending on when the mutation happened during development, they may or may not have the mutation in every cell in their body. If the mutation is in their egg or sperm, they can pass the mutation on to their children. 

What are the signs of Li-Fraumeni syndrome?

Some of the signs that may indicate Li-Fraumeni syndrome include one or more people in the family with:

• breast cancer at a very young age, especially at age 30 or younger.
• sarcoma, brain cancer, or adrenal cortical cancer, especially before age 45.
• cancers diagnosed before age 30.

This is not a complete list. FORCE recommends speaking with a genetic counselor who can help make informed decisions about genetic testing. 

How do I find out if I have Li-Fraumeni syndrome?

Genetic testing is a type of medical test that can help people learn if they have an inherited mutation in TP53 and other genes. The test can be performed on blood, saliva or tissue. The sample is collected and sent to a genetic testing lab. 

It's a good idea to speak with a genetics expert before having genetic testing. They will answer your questions about testing and ensure that the correct test is ordered. 

What are the cancer risks for people with a TP53 mutation?

People with an inherited mutation in TP53 have a very high lifetime risk for different types of cancers, including:

• brain cancer
• breast cancer
• colorectal cancer
• pancreatic cancer
• sarcomas
• other cancers

The risks for cancer begin at a very young age.

What can people do if they have Li-Fraumeni syndrome?

If you test positive for a TP53 mutation, you have options. There are expert guidelines and clinical trials that focus on:

• cancer risks with a TP53 mutation
• screening, early detection and risk-reduction

These guidelines are based on the most current research and updated yearly. People who test positive for a TP53 mutation should speak with a genetics expert to make sure that their medical care is based on the most up-to-date information. 

If you test positive for a TP53 mutation, you should inform your close blood relatives (first-, second-, and third-degree relatives) about your test results and encourage them to speak with a genetics expert.