ArticleJNCI cancer spectrum2025
Cancer risk in carriers of TP53 germline variants grouped into different functional categories.
Article in JNCI cancer spectrum, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Evaluation of non-canonical p53 functions in DNA replication and recombination for variant classification.Cell death & disease · 2026Article
- Urgent need to recognize that Disease-Causing TP53 variants with atypical penetrance require distinct clinical recommendations.Journal of the National Cancer Institute · 2026Article
- Human P53 Expression in Yeast: Investigating Its Apoptotic Effects.Mini reviews in medicinal chemistry · 2026Review
- Characteristics predicting reduced penetrance variants in the high-risk cancer predisposition gene TP53.HGG advances · 2025Article
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Authors and funding
16 authors.
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Abstract
Li-Fraumeni syndrome is a cancer predisposition syndrome caused by pathogenic TP53 germline variants; it is associated with a high lifelong cancer risk. We analyzed the German Li-Fraumeni syndrome registry, which contains data on 304 individuals. Cancer phenotypes were correlated with variants grouped according to their ability to transactivate target genes in a yeast assay using a traditional (nonfunctional, partially functional) and a novel (clusters A, B, and C) classification of variants into different groups. Partially functional and cluster B or C variants were enriched in patients who did not meet clinical testing criteria. Time to first malignancy was longer in carriers of partially functional variants (hazard ratio = 0.38, 95% CI = 0.22 to 0.66). Variants grouped within cluster B (hazard ratio = 0.45, 95% CI = 0.28 to 0.71) or C (hazard ratio = 0.34, 95% CI = 0.19 to 0.62) were associated with later cancer onset than NULL variants. These findings can be used to risk-stratify patients and inform care.
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