ArticleHuman mutation2020
A substantial proportion of apparently heterozygous TP53 pathogenic variants detected with a next-generation sequencing hereditary pan-cancer panel are acquired somatically.
Article in Human mutation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Independent somatic TP53 mutations in blood and tumor mimicking Li-Fraumeni syndrome in a 94-year-old man.NPJ precision oncology · 2026Article
- Article
- Detecting likely germline variants during tumor-based molecular profiling.The Journal of clinical investigation · 2025Review
- Clinical Significance of TP53-Mutant Clonal Hematopoiesis Across Diseases.Blood cancer discovery · 2025Article
- Clinical classification and molecular interpretation of germline pathogenic TP53 variations detected by multigene panel testing in patients with possible cancer predisposition.Molecular genetics and genomics : MGG · 2025Article
- TP53 germline testing and hereditary cancer: how somatic events and clinical criteria affect variant detection rate.Genome medicine · 2025Article
- Increased frequency of clonal hematopoiesis of indeterminate potential in Bloom syndrome probands and carriers.Haematologica · 2025Article
- Translocation of benzo(a)pyrene reactive metabolites across human mammary epithelial cell membranes.PloS one · 2025Article
- Current insights and future directions of Li-Fraumeni syndrome.Discover oncology · 2024Review
- Diagnostic and Practical Challenges in Applying National Comprehensive Cancer Network Guidelines for Suspected Pathogenic TP53 Mosaicism.JCO precision oncology · 2024Article
- Clinical outcome of pediatric medulloblastoma patients with Li-Fraumeni syndrome.Neuro-oncology · 2023Article
- Extended genetic analysis and tumor characteristics in over 4600 women with suspected hereditary breast and ovarian cancer.BMC cancer · 2023Article
- Patterns of mosaicism for sequence and copy-number variants discovered through clinical deep sequencing of disease-related genes in one million individuals.American journal of human genetics · 2023Article
- Clonal Hematopoiesis and Mosaicism Revealed by a Multi-Tissue Analysis of Constitutional TP53 Status.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2022Article
- Paired Tumor-Normal Sequencing Provides Insights Into the TP53-Related Cancer Spectrum in Patients With Li-Fraumeni Syndrome.Journal of the National Cancer Institute · 2021Article
- Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women.The New England journal of medicine · 2021Article
- Article
- Suggested application of HER2+ breast tumor phenotype for germline TP53 variant classification within ACMG/AMP guidelines.Human mutation · 2020Article
- A substantial proportion of apparently heterozygous TP53 pathogenic variants detected with a next-generation sequencing hereditary pan-cancer panel are acquired somatically.Human mutation · 2020Article
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Previous analysis of next-generation sequencing (NGS) hereditary pan-cancer panel testing demonstrated that approximately 40% of TP53 pathogenic and likely pathogenic variants (PVs) detected have NGS allele frequencies between 10% and 30%, indicating that they likely are acquired somatically. These are seen more frequently in older adults, suggesting that most result from normal aging-related clonal hematopoiesis. For this analysis, apparent heterozygous germline TP53 PV carriers (NGS allele frequency 30-70%) were offered follow-up testing to confirm variant origin. Ninety-eight probands had samples submitted for follow-up family member testing, fibroblast testing, or both. The apparent heterozygous germline TP53 PV was not detected in 32.6% (15/46) of submitted fibroblast samples, indicating that it was acquired somatically, either through clonal hematopoiesis or via constitutional mosaicism. Notably, no individuals with confirmed germline or likely germline TP53 PVs met classic Li-Fraumeni syndrome (LFS) criteria, only 41% met Chompret LFS criteria, and 59% met neither criteria, based upon provider-reported personal and family cancer history. Comprehensive reporting of TP53 PVs detected using NGS, combined with follow-up analysis to confirm variant origin, is advised for clinical testing laboratories. These findings underscore the investment required to provide individuals and family members with clinically accurate genetic test results pertaining to their LFS risk.
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