Li-Fraumeni syndrome (LFS) is a rare, autosomal-dominantly inherited cancer predisposition syndrome that was first described in 1969. LFS is associated with a wide variety of childhood- and adult-onset cancers, most notably soft-tissue and bone sarcomas, breast cancer, adrenal cortical carcinoma (ACC), brain tumors, and leukemia, with a tendency for multiple primary cancers in affected individuals. In most families, it is caused by germline mutations in the TP53 gene and is characterized by early onset of multiple specific cancers and very high lifetime cumulative cancer risk. Despite significant progress in understanding the molecular biology of TP53, the optimal clinical management of this syndrome is poorly defined. Germline mutations in the tumor suppressor gene TP53 were identified in 1990 as the cause in most families with classic LFS. The absence of detectable germline TP53 mutations in some LFS families suggests that other genes might be involved in this syndrome; however, additional other loci in LFS have not been identified.
LFS was first described in 1969 by Dr. Frederick Li and Dr. Joseph F. Fraumeni Jr. Although bone and soft tissue sarcomas, breast cancer, ACC, brain tumors, and leukemia remain the hallmarks of LFS, subsequent studies showed that the cancer spectrum was more diverse, including cancers of the lung, colorectum, stomach, prostate, ovary, pancreas, as well as lymphoma, melanoma, and choroid plexus carcinomas. The diagnostic criteria for the syndrome gradually evolved to include not only classic LFS but also Li-Fraumeni-like syndrome (LFL), which shares some features of LFS but does not meet the strict LFS diagnostic criteria.
Germline mutations in the TP53 tumor suppressor gene were discovered as the primary cause of LFS and are found in approximately 70% of LFS and 40% of LFL families. To provide guidelines for consideration of TP53 genetic testing, the Chompret criteria were proposed in 2001 and revised in 2008 and 2009. The prevalence of TP53 mutations in individuals meeting the revised Chompret criteria is approximately 30%. The prevalence of germline TP53 mutations has been estimated for some selected populations, specifically Southeastern Brazil and the United Kingdom (see Clinical aspects of LFS—a global view).
The data represented on this website includes data for families and individuals with TP53 Positive mutation testing status (from single panel tests only) and known LFS status from seven international sites, including: