{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T06:14:37Z","timestamp":1787465677917,"version":"build-2736575974"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Li\u2010Fraumeni syndrome is a rare autosomal dominant disorder caused by a pathogenic mutation of the tumor suppressor gene\n                      <jats:italic>TP53<\/jats:italic>\n                      . This disease starts at an early age and has been shown to be associated with multiple tumors. The study aims to discuss the clinical and genetic characteristics of Li\u2010Fraumeni syndrome (LFS) and to provide therapeutic experience of LFS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a retrospective analysis of the clinicopathologic features, family history, treatment and follow\u2010up in five LFS patients with germline\n                      <jats:italic>TP53<\/jats:italic>\n                      (NCBI Gene:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.ncbi.nlm.nih.gov\/gene\/7157\">7157<\/jats:ext-link>\n                      , HGNC:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.genenames.org\/data\/gene-symbol-report\/#!\/hgnc_id\/11998\">11998<\/jats:ext-link>\n                      , OMIM:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/omim.org\/entry\/191170\">191170<\/jats:ext-link>\n                      ) pathogenic\/likely pathogenic (P\/LP) variants. This research had been approved by the ethics committee and implemented.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our study involved five LFS patients with germline\n                      <jats:italic>TP53<\/jats:italic>\n                      P\/LP variants, including thyroid cancer, ovarian melanoma, colon cancer, fibrosarcoma, and lung cancer. Among this group of patients, the age at which tumors first appeared was between 24 and 53\u2009years old. Three patients had a family history of tumors, and the other two were probands in the family. Traditional chemotherapy has limited effectiveness in clinical practice and may increase the risk of tumor development. However, immune checkpoint inhibitors (ICIs) have shown unexpected efficacy in patients with high programmed cell death ligand\u20101 (PD\u2010L1) expression. Next\u2010generation sequencing (NGS) and PD\u2010L1 detection may provide more potential targets for LFS patients to achieve better therapeutic outcomes. In addition, we have added a new\n                      <jats:italic>TP53<\/jats:italic>\n                      frameshift mutation spectrum, namely c.642_643delTA (p.H214Qfs*7), which belongs to the pathogenic variant. This mutant has not been described in the existing literature.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Patients with LFS may be potential beneficiaries of immune checkpoint inhibitors and targeted therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.70177","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T13:42:11Z","timestamp":1767793331000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Features and Treatment Strategies of Li\u2010Fraumeni Syndrome Patients With Inherited\n                    <scp>TP53<\/scp>\n                    Mutations"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9066-2889","authenticated-orcid":false,"given":"Keyu","family":"Chen","sequence":"first","affiliation":[{"name":"The First Hospital of Jiaxing &amp; The Affiliated Hospital of Jiaxing University  Jiaxing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufen","family":"Xu","sequence":"additional","affiliation":[{"name":"The First Hospital of Jiaxing &amp; The Affiliated Hospital of Jiaxing University  Jiaxing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binbin","family":"Song","sequence":"additional","affiliation":[{"name":"The First Hospital of Jiaxing &amp; The Affiliated Hospital of Jiaxing University  Jiaxing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyang","family":"Gu","sequence":"additional","affiliation":[{"name":"The First Hospital of Jiaxing &amp; The Affiliated Hospital of Jiaxing University  Jiaxing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofang","family":"Xu","sequence":"additional","affiliation":[{"name":"The First Hospital of Jiaxing &amp; The Affiliated Hospital of Jiaxing University  Jiaxing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Cao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Head &amp; Neck Cancer Translational Research of Zhejiang Province, Department of Head and Neck and Rare Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM) Chinese Academy of Sciences  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiyu","family":"Fang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Head &amp; Neck Cancer Translational Research of Zhejiang Province, Department of Head and Neck and Rare Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM) Chinese Academy of Sciences  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-17-0151"},{"issue":"5","key":"e_1_2_11_3_1","first-page":"1298","article-title":"Prevalence and Diversity of Constitutional Mutations in the p53 Gene Among 21 Li\u2010Fraumeni Families","volume":"54","author":"Birch J. 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