ArticleNature communications2025
TP53 variant clusters stratify phenotypic diversity in germline carriers and reveal an osteosarcoma-prone subgroup.
Article in Nature communications, 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.
- Tumor patterns and cancer risk in carriers of TP53 exonic germline variants that alter mRNA splicing.European journal of human genetics : EJHG · 2026Article
- Urgent need to recognize that Disease-Causing TP53 variants with atypical penetrance require distinct clinical recommendations.Journal of the National Cancer Institute · 2026Article
- Transfer Learning for Survival-based Clustering of Predictors with an Application tobioRxiv : the preprint server for biology · 2025Article
- Cancer risk in carriers of TP53 germline variants grouped into different functional categories.JNCI cancer spectrum · 2025Article
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12 authors.
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Abstract
Li-Fraumeni syndrome (LFS) has recently been redefined as a 'spectrum' cancer predisposition disorder to reflect its broad phenotypic heterogeneity. This variability is thought to stem in part from the diverse functional impacts of TP53 variants, although the underlying mechanisms remain poorly understood and there is an unmet clinical need for effective risk stratification. Here, we apply unsupervised clustering to functional datasets and identify distinct TP53 variant groups with clinical relevance, including a monomeric subgroup enriched in osteosarcoma cases. In cellular validation assays, dermal fibroblasts from carriers of more functionally impaired variants exhibit increased metabolic growth rates, mirroring trends observed in cluster-stratified clinical outcomes. These findings demonstrate the feasibility of developing diagnostic assays to guide personalized cancer risk assessment. More broadly, our results show that nuances in TP53 dysfunction shape the germline TP53-related cancer susceptibility spectrum and provide a framework for functionally delineating variant carriers.
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