O15: Cancer phenotypes of hypomorphic versus non-functional TP53 variants in Li-Fraumeni syndrome

Genetics in Medicine Open 2026 Open access

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Authors: Alison Schwartz Levine, Adela Rodriguez-Hernandez, Miki Horiguchi, Isabel Anez-Bruzual, Sophie Hyman, Judy Ellen Garber, Huma Q. Rana
DOI: 10.1016/j.gimo.2026.104301
Cited by: 0

Abstract

Germline TP53 pathogenic variants (PVs) are associated with Li-Fraumeni syndrome (LFS). Recognition of TP53 variants that lead to attenuated LFS, also referred to as hypomorphic variants, has increased in recent years. These variants frequently suffer from discordant classification, leading to confusion and inconsistent or unclear management recommendations for families. Hypomorphic variants are increasingly identified through broad germline testing in individuals with cancer. They have been characterized using functional assays or reported phenotypes, but no systematic approach has leveraged detailed clinical pedigrees.

Fields of Study & Subjects

Cancer-related Molecular Pathways Genomics and Rare Diseases BRCA gene mutations in cancer

Publication details

Journal / source
Genetics in Medicine Open
Volume
4
Pages
104301–104301
Publication date
1 January 2026
Language
EN