{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T18:00:11Z","timestamp":1772992811687,"version":"3.50.1"},"reference-count":27,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Li Fraumeni syndrome (LFS) is a hereditary multi\u2010cancer syndrome caused by alterations in\n                      <jats:italic>TP53<\/jats:italic>\n                      (MIM# 151623). Next generation sequencing (NGS) allows for the detection of\n                      <jats:italic>TP53<\/jats:italic>\n                      variants at lower variant allele frequencies (VAFs). A\n                      <jats:italic>TP53<\/jats:italic>\n                      variant with a VAF\u2009&lt;\u200950% may represent mosaic LFS, aberrant clonal expansion (ACE), or possible circulating tumor DNA. Differentiation among these conditions is important for optimal patient management.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Genetic testing was performed using a custom gene panel, with an average read depth of 350\u00d7 (range 166\u2013553\u00d7). DNA extracted from four different tissues (blood, saliva, cultured skin fibroblasts, and colon) was sequenced.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Here, we describe an adult female patient with a history of an adrenocortical neoplasm and osteosarcoma, diagnosed at 2 and 16\u2009years of age, respectively. Testing of peripheral blood identified a pathogenic\n                      <jats:italic>TP53<\/jats:italic>\n                      variant, c.733G&gt;A, p.(Gly245Ser) (NM_000546.6); however, subsequent in\u00a0vitro fertilization with preimplantation genetic testing for monogenic disorders (PGT\u2010M) did not identify this\n                      <jats:italic>TP53<\/jats:italic>\n                      variant in any of nine embryos tested. Testing for possible mosaicism in the proband was performed on four different specimens, revealing variable VAFs of the\n                      <jats:italic>TP53<\/jats:italic>\n                      variant (saliva: 44%; blood: 31%; cultured skin fibroblasts: 18%; and colon tissue: 9%). These results suggest a post\u2010zygotic event, consistent with mosaic LFS rather than ACE.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This case highlights the complexity of interpreting mosaic variants in the\n                      <jats:italic>TP53<\/jats:italic>\n                      gene, and we propose a testing algorithm to aid in the delineation of this phenomenon when relaying cancer and reproductive risk information in the context of mosaicism.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.70178","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T07:31:34Z","timestamp":1769758294000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mosaic Li Fraumeni Syndrome Not Identified in Germinal Tissue"],"prefix":"10.1002","volume":"14","author":[{"given":"Rhianna M.","family":"Urban","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nisha","family":"Kanwar","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan A.","family":"Holdren","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan F.","family":"Hoenig","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura M.","family":"Rust","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myra J.","family":"Wick","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew J.","family":"Ferber","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiyv","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sounak","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3779-0451","authenticated-orcid":false,"given":"Wei","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,29]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13058\u2010019\u20101193\u20101"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2015.249623"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.38.4.253"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2015.03.013"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436\u2010021\u201001138\u20105"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergen.2017.01.002"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2017.07.010"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2023.0051"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1200\/PO.20.00064"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1705823"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1431692100"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2005.01.026"},{"issue":"6","key":"e_1_2_12_14_1","first-page":"1365","article-title":"Rhabdomyosarcoma in Children: Epidemiologic Study and Identification of a Familial Cancer Syndrome","volume":"43","author":"Li F. 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