What Is Li-Fraumeni Syndrome, and Where Does Its Name Come From?

Associated with germline (inherited) TP53 mutations, Li-Fraumeni syndrome is a rare hereditary cancer syndrome.

Patients with Li-Fraumeni syndrome typically develop cancer at a young age and have an increased lifetime risk of developing multiple cancers.

Li-Fraumeni syndrome is most commonly associated with sarcoma, breast cancer, adrenocortical (adrenal gland) tumors, and certain brain tumors. It has also been associated with colon and stomach cancers, hypodiploid acute lymphoblastic leukemia, and other cancers.

All patients with Li-Fraumeni syndrome and their families are recommended to undergo syndrome-specific cancer screening and follow-up as soon as diagnosed, as advised in hereditary cancer guidance.

The History of the Name Li-Fraumeni

Dr. Frederick P. Li and Dr. Joseph F. Fraumeni are the namesakes of Li-Fraumeni syndrome. 

Dr. Li was born in Canton, China, in 1940. At age 16, he enrolled at New York University and earned a degree in physics. He studied medicine at Rochester University, received a master’s degree in demography from Georgetown University, and began working at the US National Cancer Institute (NCI) in 1967.

Dr. Fraumeni was born in Boston in 1933. He earned his undergraduate degree at Harvard College, completed medical training at Duke University, and joined the NCI in 1962. 

Early in his career, Dr. Fraumeni and NCI colleague Robert W. Miller began exploring epidemiological patterns of childhood and hereditary cancer. Their study of children with Wilms tumor revealed congenital abnormalities and family members with histories of Wilms tumor and other cancers.

Dr. Fraumeni also investigated several “cancer-prone families,” forming the basis of the familial cancer registry in the NCI’s Cancer Epidemiology and Genetics division. Separately, Dr. Li encountered a family in which several members developed different cancers as children and young adults. 

Dr. Li and Fraumeni formed a team and published a study of 4 families with a “high frequency of cancer” in 1969. Between 1969 and 1981, 16 additional cancers developed in 10 of the 31 surviving family members.

The term “Li-Fraumeni syndrome” was coined in 1982 by UK researchers reporting findings in 2 cancer-prone families.

In a 1988 study, Dr. Li, Dr. Fraumeni, and colleagues assessed 24 similar families and described classic Li-Fraumeni syndrome: “A person with sarcoma before age 45 was designated the proband (target/first patient); a first-degree relative with cancer in this age range; and another close relative (first- or second-degree) with cancer in this age range or sarcoma at any age.”

In 1990, researchers discovered that germline (inherited) TP53 mutations cause Li-Fraumeni syndrome. Later studies suggested that CHEK2 mutations are also linked to Li-Fraumeni syndrome.

• Related topic: What are the TP53 gene and p53 protein? What does a positive TP53 mutation result mean in cancer?

After researchers discovered the link between TP53 and Li-Fraumeni syndrome, Dr. Li helped establish a center at Dana-Farber Cancer Institute to test people for inherited cancer risks. The NCI had sent him to Dana-Farber in the early 1970s, and he spent more than 30 years there.

Dr. Li became head of Dana-Farber’s Cancer Epidemiology and Control division in 1991. He retired in 2008 and died from complications of Alzheimer’s disease in 2015 at age 75.

Dr. Fraumeni remained at the NCI for nearly his entire career. He spent an academic year at Harvard School of Public Health, earning a master’s degree in 1965. He was founding director of the Division of Cancer Epidemiology and Genetics in 1995. He became its director in 2012 and remained a senior adviser until retiring in 2017.