{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:02:00Z","timestamp":1784246520068,"version":"3.55.0"},"reference-count":41,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30 CA177558"],"award-info":[{"award-number":["P30 CA177558"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20 GM121327"],"award-info":[{"award-number":["P20 GM121327"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Kentucky Pediatric Cancer Research Trust Fund"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    We identified a germline\n                    <jats:italic>TP53<\/jats:italic>\n                    c.758C\u2009&gt;\u2009T (p.T253I) mutation in the\n                    <jats:italic>TP53<\/jats:italic>\n                    tumor suppressor gene in a pediatric adrenocortical carcinoma (ACC) patient. Characteristic of pathogenic p53 mutations, we observed upregulation of total p53 protein levels in the patient\u2019s ACC and concurrent suppression of the wild-type (WT)\n                    <jats:italic>TP53<\/jats:italic>\n                    allele. As ACC can be associated with Li-Fraumeni Syndrome (LFS) and the mutation has not yet been linked to LFS, we sought to characterize the functionality of the T253I mutation. We acquired p53\n                    <jats:sup>-\/-<\/jats:sup>\n                    HEK293 cells and stably transduced them with GFP-tagged wild type (T253) or T253I p53 as well as two established pathogenic p53 mutants (C176Y and R213X). Compared to p53 WT, levels of T253I p53 increased while MDM2 levels decreased, suggesting a loss of MDM2-mediated regulation of T253I p53. Additionally, T253I showed a reduction in DNA damage responsive events, diminished DNA binding capabilities, and blunted transactivation capacity. These experimental data lead us to conclude that T253I represents a pathologic variant in\n                    <jats:italic>TP53<\/jats:italic>\n                    that may predispose to LFS-associated tumors.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0320036","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T18:33:41Z","timestamp":1764959621000},"page":"e0320036","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Characterization of p53 p.T253I as a pathogenic mutation underlying Li-Fraumeni Syndrome"],"prefix":"10.1371","volume":"20","author":[{"given":"Nathaniel C.","family":"Holcomb","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda M.","family":"Harrington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Pu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berina","family":"Halilovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan R.","family":"Shelman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shulin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Sears","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terra","family":"Armstrong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brent","family":"Shelton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Corum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1008-6234","authenticated-orcid":true,"given":"John A.","family":"D'Orazio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"issue":"4","key":"pone.0320036.ref001","doi-asserted-by":"crossref","first-page":"747","DOI":"10.7326\/0003-4819-71-4-747","article-title":"Soft-tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome?","volume":"71","author":"FP Li","year":"1969","journal-title":"Ann Intern Med"},{"key":"pone.0320036.ref002","article-title":"Li-Fraumeni Syndrome.","volume-title":"GeneReviews(R)","author":"K Schneider","year":"1993"},{"issue":"4","key":"pone.0320036.ref003","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1097\/CCO.0000000000000200","article-title":"Surveillance recommendations for patients with germline TP53 mutations","volume":"27","author":"ML Ballinger","year":"2015","journal-title":"Curr Opin Oncol"},{"issue":"2","key":"pone.0320036.ref004","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1055\/s-0036-1579759","article-title":"Li-Fraumeni Syndrome","volume":"5","author":"H Correa","year":"2016","journal-title":"J Pediatr Genet"},{"issue":"2","key":"pone.0320036.ref005","first-page":"83","article-title":"Germ-line p53 mutations predispose to a wide spectrum of early-onset cancers","volume":"10","author":"KE 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Gargallo","year":"2020","journal-title":"Clin Transl Oncol"},{"issue":"6","key":"pone.0320036.ref009","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/S1470-2045(11)70119-X","article-title":"Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: a prospective observational study","volume":"12","author":"A Villani","year":"2011","journal-title":"Lancet Oncol"},{"issue":"9","key":"pone.0320036.ref010","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1016\/S1470-2045(16)30249-2","article-title":"Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: 11 year follow-up of a prospective observational study","volume":"17","author":"A Villani","year":"2016","journal-title":"Lancet Oncol"},{"issue":"7696","key":"pone.0320036.ref011","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/nature25480","article-title":"The landscape of genomic alterations across childhood 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