Analysis of the Li-Fraumeni Spectrum Based on an International Germline TP53 Variant Data Set

Key Points Questions What is the phenotypic spectrum associated with variants in TP53, the gene variant in persons with Li-Fraumeni syndrome, and what mechanisms underlie phenotypic differences? Findings In this cohort study, the phenotypes within the classification Li-Fraumeni spectrum were defined, and data from 3034 persons from 1282 families with data available in the International Agency for Research on Cancer TP53 Database were analyzed and classified to reveal meaningful differences in the TP53 variant distribution between patients who met vs those who did not meet Li-Fraumeni syndrome testing criteria. Meaning The study results suggest that this classification is a potential step toward understanding the factors that lead to phenotypic differences in the Li-Fraumeni spectrum and may serve as a model for the reclassification of other hereditary conditions with an increased cancer risk.

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