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Onc."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Accurately determining the origin of\n                    <jats:italic>TP53<\/jats:italic>\n                    variants detected in blood is essential as such variants may arise from the constitutional state or clonal hematopoiesis (CH). While paired tumor-blood sequencing is widely used to distinguish somatic from constitutional events, convergent acquisition of identical\n                    <jats:italic>TP53<\/jats:italic>\n                    hotspot mutations in tumor and blood can obscure variant origin and complicate interpretation. Here we report a 94-year-old patient with the\n                    <jats:italic>TP53<\/jats:italic>\n                    c.524\u2009G\u2009&gt;\u2009A (p.Arg175His) pathogenic variant identified in both peripheral blood and tumor tissue, initially raising concern for Li-Fraumeni syndrome (LFS). Given the patient\u2019s atypical LFS clinical presentations, multi-tissue confirmatory analysis was performed. Normal bladder tissue and skin biopsy each showed trace mutant signal, and fingernail DNA was negative. These findings support independent somatic acquisition of the same\n                    <jats:italic>TP53<\/jats:italic>\n                    hotspot mutation in hematopoietic and tumor lineages. This case highlights the importance of multi-tissue confirmatory testing to accurately determine the origin of\n                    <jats:italic>TP53<\/jats:italic>\n                    variants in cancer patients.\n                  <\/jats:p>","DOI":"10.1038\/s41698-026-01544-5","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T19:06:24Z","timestamp":1780945584000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Independent somatic TP53 mutations in blood and tumor mimicking Li-Fraumeni syndrome in a 94-year-old man"],"prefix":"10.1038","volume":"10","author":[{"given":"Chuan","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikas","family":"Rai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zarina","family":"Yelskaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvana","family":"Ostafi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Somar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neal","family":"Cody","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panieh","family":"Terraf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maksym","family":"Misyura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozge","family":"Ceyhan-Birsoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Mandelker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"key":"1544_CR1","first-page":"5358","volume":"48","author":"FP Li","year":"1988","unstructured":"Li, F. P. et al. A cancer family syndrome in twenty-four kindreds. Cancer Res. 48, 5358\u20135362 (1988).","journal-title":"Cancer Res."},{"key":"1544_CR2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s10689-020-00207-z","volume":"20","author":"DG Evans","year":"2021","unstructured":"Evans, D. G. & Woodward, E. R. New surveillance guidelines for Li-Fraumeni and hereditary TP53 related cancer syndrome: implications for germline TP53 testing in breast cancer. Fam Cancer 20, 1\u20137 (2021).","journal-title":"Fam Cancer"},{"key":"1544_CR3","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1097\/CCO.0000000000000423","volume":"30","author":"A Amadou","year":"2018","unstructured":"Amadou, A., Achatz, M. I. W. & Hainaut, P. Revisiting tumor patterns and penetrance in germline TP53 mutation carriers: temporal phases of Li-Fraumeni syndrome. 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