Guardian of the Genome: An Overview of Li-Fraumeni Syndrome

Li-Fraumeni syndrome

Li-Fraumeni syndrome

When I was initially diagnosed with Lynch syndrome, I became highly interested in other hereditary cancer syndromes and wanted to learn as much about them as I could. Reading about them gave me tremendous perspective. The more I read, the more I recognized the parallels between them … there may be some different cancer manifestations of these syndromes but for the most part the emotional gravity of having a hereditary cancer syndrome is the same.


You may be familiar with the BRCA genes and Lynch syndrome, but there are many other cancer predisposition syndromes that affect people around the world. One such condition is Li-Fraumeni syndrome – a rare syndrome that affects about 1 in 20,000 people. Li-Fraumeni syndrome was identified by Dr. Frederick Li and Dr. Joseph Fraumeni in 1969. The two doctors noted a number of families affected by multiples types of cancer and cancers that developed at a young age. Their research of these notable families ultimately led to the discovery of a new cancer predisposition syndrome and the gene responsible for the condition.

What is Li-Fraumeni Syndrome?

Li-Fraumeni syndrome is an inherited condition that increases a person’s risk for a wide range of cancers. Individuals with Li-Fraumeni syndrome are at risk for the following types of cancer:

  • Pre-menopausal breast cancer
  • Brain tumors
  • Soft tissue sarcomas
  • Bone sarcomas
  • Adrenal cortical tumors
  • Leukemia
  • Melanoma
  • Gastrointestinal cancers (colon, stomach, pancreas)

Li-Fraumeni syndrome affects both men and women, although women are more likely to develop cancer due to the risk for breast cancer. Individuals with Li-Fraumeni syndrome have a high risk for developing multiple primary cancers during their lifetime. There is also a higher likelihood of developing cancer at a younger age than expected. Cancers may occur in young adulthood, or even as early as childhood. The risk for childhood cancers, such as brain tumors and leukemia, makes Li-Fraumeni syndrome distinct from other cancer predisposition syndromes.

What causes Li-Fraumeni Syndrome?

Li-Fraumeni is caused by mutations in the TP53 gene. TP53 is one of many tumor suppressor genes that help protect our bodies from cancer. This gene contains the instructions for the body to make “tumor protein 53”, also known as “p53”. P53 is responsible for fixing errors that arise during the process of cell division. This protein works in different types of cells throughout our entire body, making it very important. Because of its critical functions, p53 has been called “the guardian of the genome.”

In Li-Fraumeni syndrome, a person is born with a mutation in TP53 that prevents the gene from working like it is supposed to. It is natural for our bodies to make errors during the process of cell division. Certain environmental exposures, such as UV rays from the sun, may also cause damage in our cells. Typically, the p53 protein can fix these mistakes. When someone has a mutation in TP53, there is not enough p53 protein to catch all of the errors that can happen. This means there is a higher chance for cells to continuing growing abnormally following a mistake, which can ultimately lead to cancer.

What is the medical management for Li-Fraumeni syndrome?

The medical community has established several screening guidelines to help reduce the risk for cancer in Li-Fraumeni patients. Because of the multitude of cancer risks, a newly diagnosed patient should meet with a genetic counselor and appropriate specialists to develop an individualized screening plan. In general, annual whole body MRIs are recommended to thoroughly check for tumors. Radiation exposure, including radiation therapy, should be kept to a minimum. Some of the screening guidelines for Li-Fraumeni syndrome overlap with BRCA1/2 and Lynch syndrome, due to the risk for early-onset breast cancer and colon cancer.

How is Li-Fraumeni syndrome inherited?

Every person has two copies of the TP53 gene – one inherited from their mother, and one inherited from their father. A person who has Li-Fraumeni syndrome has a mutation in one copy of the TP53 gene. In other words, it is an autosomal dominant condition. Someone with Li-Fraumeni syndrome has a 50% chance of passing on the copy of TP53 with the mutation to each of their children. There is also a 50% chance that parents and siblings have the same mutation.

Most cases of Li-Fraumeni syndrome are familial and a strong family history of cancer is observed. Individuals diagnosed with Li-Fraumeni syndrome usually inherited the gene mutation from either their mother or father. In up to 20%of cases, the condition is caused by a new or “de novo” mutation. This means the patient is the first person in the family to have Li-Fraumeni syndrome, and there may be no other family history of cancer.

Who should have testing for Li-Fraumeni syndrome?

Genetic testing for Li-Fraumeni syndrome is typically offered to people who meet any of the following criteria:

  • Women who have had breast cancer prior to age 30 (especially if BRCA1 and BRCA2 genetic testing was negative)
  • Individuals who have had adrenocortical carcinoma (a type of tumor found in a gland above the kidney)
  • Individuals who have had choroid plexus carcinoma (a rare type of childhood brain tumor)
  • Individuals who have had any Li-Fraumeni associated cancer diagnosed before age 46 AND have at least one close relative also diagnosed with a Li-Fraumeni cancer
  • Individuals who have had two or more types of cancer associated with Li-Fraumeni, with the first being diagnosed prior to age 46

Testing for Li-Fraumeni syndrome is also recommended when there is a known TP53 mutation in the family. Unlike most inherited cancer syndromes, genetic testing for TP53 is warranted for children. This is because of the increased risk for childhood cancers. Screening for cancers can start at an earlier age, so it is helpful to know if children and young adults have a mutation. In other inherited cancer syndromes, genetic testing for a familial mutation is not usually recommended until a child turns 18 and can make their own medical decisions. It can be difficult for parents to decide when to have their children tested, as this information will impact the rest of their lives. A genetic counselor can help with this discussion, as the most appropriate timing varies for every family.

Genetic testing for TP53 is available through several commercial laboratories. Individuals who seek genetic testing should request an appointment with a genetic counselor to learn more about inherited cancer syndromes and to discuss the benefits, risks and limitations of genetic testing.

Version 2

Rebecca is a second year graduate student at the Northwestern University Graduate Program in Genetic Counseling. She is simultaneously pursuing a masters degree in medical humanities and bioethics at Northwestern. Rebecca originally hails from the San Francisco Bay Area and worked at a genetic testing laboratory prior to graduate school. In her free time, she enjoys hiking, cooking, and trying new workout classes.

Pathway’s genetic tests screen a number of known genes related to hereditary cancers. The goal of every test is to determine a patient’s risk of cancer. This knowledge can help your physician to develop the appropriate or preventative treatment plan for early detection. If the results of your test indicate an increased risk for cancer, your doctor may order tests like mammograms, colonoscopy and CT scans for any possible diagnosis and immediate intervention.

Pathway Genomics provides genetic testing for Li-Fraumeni syndrome. Please ask your doctor and certified genetic counselor if you are a candidate for genetic testing.

I recently hosted the Pink and Blue: Colors of Hereditary Cancer in Chicago on December 1st! We had a great turn out and my #GenCSM partners, Amy Byer Shainman and Ellen Matloff, attended the event! I would like to thank them and Dr. Liu and Scott Weissman, CGC, for being on the stellar Q & A panel! Gratitude to Pathway Genomics for sponsoring the screening in Chicago!








We recently also had our #GenCSM tweet chat with thee Dr. Siddhartha Mukherjee and it was our most successful #GenCSM chat to date! Dr. Mukherjee was very gracious to spend an hour with us, answering our questions and addressing questions from the audience.

Please click here to read the transcript! Again, gratitude to Pathway Genomics for sponsoring it!

Together we are raising awareness and truly saving lives!





Happy Holidays to you and yours and may your New Year be filled with health, happiness, and love.


Georgia Hurst

Founder and Executive Director of




comments powered by Disqus

Recent Tweets

Genetic Counsel Twitter Topic
My Gene Counsel Web Linked Image
BRC Ad Link




Chicago Genetics Consultants
Chicago Genetics Consultants