Cancer Predisposition in Li-Fraumeni Syndrome

Abstract

Li-Fraumeni syndrome (LFS) is a heritable highly penetrant cancer predisposition syndrome caused primarily by germline pathogenic variants in the TP53 tumor suppressor gene. Individuals with LFS have a lifetime cancer risk approaching 100% and a broad phenotypic heterogeneity in age of onset and tumor subtype. Advances in our understanding of TP53 biology and the broad phenotypic spectrum have enhanced our insight into genotype–phenotype correlations in LFS. The role of surveillance and early detection has been crucial to improving the outcomes of those living with LFS; however, prevention and tumor interception are emerging as the next step to focus on in future studies. This review discusses the broad phenotypic spectrum of LFS, genotype–phenotype correlations, the biology of TP53, early detection through clinical surveillance, and newborn screening as the next frontiers of cancer prevention and early cancer interception.