Eponyms in Oncology: Li-Fraumeni Syndrome


This weekly series highlights eponyms in oncology. This week, we explore the history and namesakes of Li-Fraumeni syndrome.

Li-Fraumeni syndrome is a rare hereditary cancer syndrome associated with germline TP53 mutations.1

Patients with Li-Fraumeni syndrome typically develop cancers at a young age but have an increased risk of developing multiple cancers throughout their lifetimes.


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Li-Fraumeni syndrome is most commonly associated with sarcoma, breast cancer, adrenocortical tumors, and certain brain tumors. However, the syndrome has been linked to colon and gastric cancers, hypodiploid acute lymphoblastic leukemia, and other cancers.

Experts have recommended that all patients with Li-Fraumeni syndrome be offered cancer surveillance as soon as the syndrome is diagnosed.2 

History of the Name

Frederick P. Li, MD, and Joseph F. Fraumeni, Jr, MD, are the namesakes of Li-Fraumeni syndrome. 

Dr Li was born in Canton, China, in 1940.3 He enrolled at New York University at the age of 16 and earned a degree in physics. He studied medicine at the University of Rochester, earned a master’s degree in demography from Georgetown University, and began working at the National Cancer Institute (NCI) in 1967.

Dr Fraumeni was born in Boston in 1933.4 He received his bachelor’s degree from Harvard College, completed his medical education at Duke University, and joined the NCI in 1962. 

Early in his career, Dr Fraumeni and a colleague at the NCI, Robert W. Miller, PhD, began exploring the epidemiologic patterns of childhood and hereditary cancer.5 The pair conducted a study of children with Wilm’s tumor that revealed congenital anomalies in these patients as well as family members with a history of Wilm’s tumor and other cancers.6

Dr Fraumeni also began to investigate a series of “cancer-prone families,” who became the foundation for the NCI’s Division of Cancer Epidemiology & Genetics familial cancer registry.5 Separately, Dr Li encountered a family in which several members developed different cancers as children and young adults. 

Drs Li and Fraumeni teamed up and, in 1969, published a study of 4 families with “a high frequency of cancer.”7 Between 1969 and 1981, 10 of the 31 surviving family members developed 16 additional cancers.8 

The term “Li-Fraumeni syndrome” was coined in 1982 by a group of researchers in the United Kingdom when reporting findings on 2 families with a predisposition to cancers.9 

In a 1988 study, Dr Li, Dr Fraumeni, and their colleagues evaluated 24 similar families and described what has become known as classical Li-Fraumeni syndrome: “one individual, designated the proband, with a sarcoma before 45 years of age; a first degree relative with cancer in this age interval; and another close (first or second degree) relative in the lineage with either cancer at this age interval or a sarcoma at any age.”10

In 1990, the researchers discovered that germline TP53 mutations were the cause of Li-Fraumeni syndrome.11 Subsequent studies suggested a link between CHEK2 mutations and Li-Fraumeni syndrome as well.12,13

After the researchers discovered the link between TP53 and Li-Fraumeni syndrome, Dr Li helped create a center at the Dana-Farber Cancer Institute to test people for inherited risks for cancer.14 Dr Li had been sent to Dana-Farber by the NCI in the early 1970s, and he spent more than 30 years there.3

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

Dr Fraumeni remained at the NCI for nearly all of his career.4,15 He did spend an academic year at the Harvard School of Public Health, where he received an MSc degree in 1965. Dr Fraumeni was the founding director of the Division of Cancer Epidemiology & Genetics in 1995. In 2012, he stepped down as director but remained a senior advisor until his retirement in 2017. 

References

  1. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology. Genetic/familial high-risk assessment: Breast, ovarian and pancreatic. Version 2.2022. Published March 9, 2022. Accessed April 29, 2022. https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf
  2. Kratz CP, Achatz MI, Brugieres L, et al. Cancer screening recommendations for individuals with Li-Fraumeni syndrome. Clin Cancer Res. 2017;23(11):e38–e45. doi:10.1158/1078-0432.CCR-17-0408
  3. Grady D. Frederick P. Li, who proved a genetic cancer link, dies at 75. New York Times. Published June 21, 2015. Accessed April 29, 2022. https://www.nytimes.com/2015/06/22/health/frederick-p-li-who-proved-a-genetic-cancer-link-dies-at-75.html?smprod=nytcore-iphone&smid=nytcore-iphone-share&_r=2
  4. Hoover RN. A conversation with Joseph F. Fraumeni, Jr. Epidemiology. 2013;24(6):929-33. doi:10.1097/EDE.0b013e3182a56987
  5. How a multicancer hereditary syndrome was discovered. Division of Epidemiology and Genetics, National Cancer Institute. Published February 15, 2013. Accessed April 29, 2022. https://dceg.cancer.gov/news-events/news/2013/hereditary-multicancer-syndrome
  6. Miller RW, Fraumeni JF Jr, Manning MD. Association of Wilms’s tumor with aniridia, hemihypertrophy and other congenital malformations. N Engl J Med. 1964;270:922–927. doi:10.1056/NEJM196404302701802
  7. Li FP, Fraumeni JF, Jr. Soft-tissue sarcomas, breast cancer, and other neoplasms: A familial syndrome? Ann Intern Med. 1969;71(4):747-52. doi:10.7326/0003-4819-71-4-747
  8. Li FP, Fraumeni JF, Jr. Prospective study of a family cancer syndrome. JAMA. 1982;247:2692-94. doi:10.1001/jama.1982.03320440040031
  9. Pearson ADJ, Craft AW, Ratcliffe JM, et al. Two families with the Li-Fraumeni cancer family syndrome. J Med Genet. 1982;19(5): 362–365. doi:10.1136/jmg.19.5.362
  10. Li FP, Fraumeni JF, Jr, Mulvhill JJ, et al. A cancer family syndrome in twenty-four kindreds. Cancer Res. 1988;48:5358-5362. 
  11. Malkin D, Li FP, Strong LC, et al. Germline p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science. 1990;250:1233–8. doi:10.1126/science.1978757
  12. Evans DG, Birch JM, Narod SA. Is CHEK2 a cause of the Li-Fraumeni syndrome? J Med Genet. 2008;45(1):63-4. doi:10.1136/jmg.2007.054700
  13. Ruijs MWG, Broeks A, Menko FH, et al. The contribution of CHEK2 to the TP53-negative Li-Fraumeni phenotype. Hered Cancer Clin Pract. 2009;7(1):4. doi:10.1186/1897-4287-7-4
  14. Feldscher K. In memoriam: Fred Li, pioneer of population cancer genetics. Accessed April 29, 2022. https://www.hsph.harvard.edu/news/features/in-memoriam-fred-li-pioneer-of-population-cancer-genetics/
  15. Joseph M. Fraumeni, MD. Division of Epidemiology and Genetics, National Cancer Institute. Accessed April 29, 2022. https://dceg.cancer.gov/about/staff-directory/fraumeni-joseph



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