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Li-Fraumeni Syndrome

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The Hereditary Basis of Childhood Cancer

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Abstract

Li-Fraumeni syndrome (LFS) is a prototypic cancer susceptibility syndrome, resulting from germline pathogenic variants in the tumor suppressor gene, TP53. Originally described in 1969 (Li, Fraumeni, Jr. Annals of Internal Medicine. 71:747–752) as a familial syndrome characterized by soft tissue sarcoma, breast cancer, and other neoplasms in children and young adults, work over the ensuing decades has led to the recognition of an expanded phenotype of early-onset cancers with varying degrees of aggressiveness. The marked clinical heterogeneity in site and age of cancer onset represents one of the challenges inherent in managing patients with this syndrome. Advances in our understanding of the genomic basis of LFS will play an important role in refining genotype-phenotype correlations within and between LFS families. Furthermore, it can also be expected that the role of p53 in human cancer generally will be more clearly articulated through the ongoing study of the progression to cancer in these patients. This chapter will summarize the current state of the art in the study and genetics-based management of LFS.

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Acknowledgments

This work was supported in part by funds from the Canadian Institutes for Health Research (Grant #143234) and Terry Fox Research Institute (#1081).

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  1. Hematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada

    Anita Villani & David Malkin

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  1. Anita Villani
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  2. Thierry Frebourg
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Correspondence to David Malkin .

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  1. University of Toronto, Departments of Pediatrics and Medical Biophysics, The Hospital for Sick Children, Division of Hematology/Oncology, Toronto, ON, Canada

    David Malkin

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Villani, A., Frebourg, T., Malkin, D. (2021). Li-Fraumeni Syndrome. In: Malkin, D. (eds) The Hereditary Basis of Childhood Cancer. Springer, Cham. https://doi.org/10.1007/978-3-030-74448-9_1

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