ArticleGenetics in medicine : official journal of the American College of Medical Genetics2018
Somatic TP53 variants frequently confound germ-line testing results.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 3 of them syntheses that pooled it.
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81 citing papers in PubMed, 3 syntheses or guidelines pooled it, 123 citations in OpenAlex.
- Somatic and germline genetic testing pathways in haematological malignancies: Best practice consensus guidelines from the 2025 national meeting organised by UK Cancer Genetics Group (UKCGG), CanGene-CanVar and the NHS England Haematological Oncology Working Group.British journal of haematology · 2026Guideline
- Germline and somatic testing for homologous repair deficiency in patients with prostate cancer (part 1 of 2).Prostate cancer and prostatic diseases · 2025Guideline
- SEOM clinical guideline on heritable TP53-related cancer syndrome (2022).Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Guideline
- Trial
- Independent somatic TP53 mutations in blood and tumor mimicking Li-Fraumeni syndrome in a 94-year-old man.NPJ precision oncology · 2026Article
- Genotypic and phenotypic characteristics of germline TP53 variant carriers: experience from two cancer genetic counseling units.Familial cancer · 2026Article
- Quality and Safety Imperatives in the Identification and Management of Hereditary Cancer Syndromes.Seminars in oncology nursing · 2026Review
- Proposed framework for triage of putative germline variants detected via tumour genomic testing in UK oncology practice.Journal of medical genetics · 2025Article
- Clonal hematopoiesis of indeterminate potential: a multisystem hub bridging hematopoietic dysfunction with non-hematopoietic diseases.Military Medical Research · 2025Review
- PYNNACLE phase II clinical trial protocol: rezatapopt (PC14586) monotherapy in advanced or metastatic solid tumors with aFuture oncology (London, England) · 2025Article
- Detecting likely germline variants during tumor-based molecular profiling.The Journal of clinical investigation · 2025Review
- Low Allele Frequency Variants Identified on Germline Multi-Gene Panel Testing for Cancer Predisposition Can Suggest the Presence of Constitutional Mosaicism.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Deciphering TP53 Mosaic Variants on Germline Biomarker Testing: Implications for Oncology Nurses.Clinical journal of oncology nursing · 2025Article
- Myelodysplastic syndrome diagnosed by genetic testing for hereditary cancer: a case report.NPJ genomic medicine · 2025Article
- Risk of lymphoid malignancy associated with cancer predisposition genes.Blood cancer journal · 2025Article
- TP53 germline testing and hereditary cancer: how somatic events and clinical criteria affect variant detection rate.Genome medicine · 2025Article
- Pathogenic Variants in Cancer Susceptibility Genes Predispose to Ductal Carcinoma In Situ of the Breast.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- A comprehensive framework for the management of hereditary breast cancers: guiding light in precision medicine.Oncology reviews · 2025Review
- [The role of clonal hematopoiesis in the molecular diagnostics of solid tumors].Magyar onkologia · 2024Review
- Pedigree analysis exploring the inconsistency between diverse phenotypes and testing criteria for germline TP53 mutations in Chinese women with breast cancer.Breast cancer research and treatment · 2024Article
21 more citing papers are in PubMed but not listed here.
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18 authors at 3 institutions in 1 country.
Funding
Abstract
purposeBlood/saliva DNA is thought to represent the germ line in genetic cancer-risk assessment. Cases with pathogenic TP53 variants detected by multigene panel testing are often discordant with Li-Fraumeni syndrome, raising concern about misinterpretation of acquired aberrant clonal expansions (ACEs) with TP53 variants as germ-line results.
methodsPathogenic TP53 variants with abnormal next-generation sequencing metrics (e.g., decreased ratio (<25%) of mutant to wild-type allele, more than two detected alleles) were selected from a CLIA laboratory testing cohort. Alternate tissues and/or close relatives were tested to distinguish between ACE and germ-line status. Clinical data and Li-Fraumeni syndrome testing criteria were examined.
resultsAmong 114,630 multigene panel tests and 1,454 TP53 gene-specific analyses, abnormal next-generation sequencing metrics were observed in 20% of 353 TP53-positive results, and ACE was confirmed for 91% of cases with ancillary materials, most of these due to clonal hematopoiesis. Only four met Chompret criteria. Individuals with ACE were older (50 years vs. 33.7; P = 0.02) and were identified more frequently in multigene panel tests (66/285; 23.2%) than in TP53 gene-specific tests (6/68; 8.8%, P = 0.005).
conclusionACE confounds germ-line diagnosis, may portend hematologic malignancy, and may provoke unwarranted clinical interventions. Ancillary testing to confirm germ-line status should precede Li-Fraumeni syndrome management.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.