{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:05:01Z","timestamp":1790255101714,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004699","name":"Chung Shan Medical University Hospital","doi-asserted-by":"publisher","award":["CSH\u20102023\u2010C\u2010016, CSH\u20102024\u2010C\u2010012, and CSH\u20102026\u2010C\u2010009"],"award-info":[{"award-number":["CSH\u20102023\u2010C\u2010016, CSH\u20102024\u2010C\u2010012, and CSH\u20102026\u2010C\u2010009"]}],"id":[{"id":"10.13039\/501100004699","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp;amp; Cancer"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Neuroendocrine carcinoma (NEC) of the uterine cervix is a rare, highly aggressive malignancy with a poor prognosis. Expanding upon our previous work, which identified frequent mutations in\n                      <jats:italic>HER2<\/jats:italic>\n                      ,\n                      <jats:italic>KRAS<\/jats:italic>\n                      , and\n                      <jats:italic>PIK3CA<\/jats:italic>\n                      in this disease, we sought to refine the genomic landscape by characterizing alterations in\n                      <jats:italic>TP53<\/jats:italic>\n                      and\n                      <jats:italic>PTEN<\/jats:italic>\n                      , and their relationships with these oncogenic drivers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Genomic DNA from 12 cervical NECs with \u2265\u200950% tumor cellularity underwent targeted next\u2010generation sequencing (NGS) using the Qiagen GeneRead DNAseq Targeted Panels V2. Variants were filtered against COSMIC and ClinVar, and the pathogenicity of missense changes was assessed with PolyPhen\u20102, with scores &gt;\u20090.85 considered probably damaging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>PTEN<\/jats:italic>\n                      alterations were identified in 25.0% (3\/12) of tumors, encompassing four truncating mutations (p.W111*, p.Q171*, p.Q245*, p.R335*) and three missense variants (p.R130Q, p.E394G, p.D395V). A\n                      <jats:italic>TP53<\/jats:italic>\n                      DNA\u2010binding domain hotspot mutation, p.R273H, was detected in 8.33% (1\/12). These tumor\u2010suppressor lesions frequently co\u2010occurred with oncogenic driver mutations, including\n                      <jats:italic>HER2\/PTEN<\/jats:italic>\n                      (8.33%),\n                      <jats:italic>PIK3CA\/PTEN<\/jats:italic>\n                      (8.33%), and a\n                      <jats:italic>KRAS\/PTEN\/TP53<\/jats:italic>\n                      \u201ctriple\u2010hit\u201d (8.33%), underscoring multipathway genomic complexity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our findings suggest a genomic landscape consistent with a multihit hypothesis in cervical NEC, in which disruption of the reciprocal tumor\u2010suppressive PTEN\u2010p53 axis (25.0% and 8.33%, respectively) co\u2010occurs with oncogenic\n                      <jats:italic>HER2<\/jats:italic>\n                      ,\n                      <jats:italic>KRAS<\/jats:italic>\n                      , or\n                      <jats:italic>PIK3CA<\/jats:italic>\n                      alterations. Structural mapping indicates that\n                      <jats:italic>TP53<\/jats:italic>\n                      p.R273H gain\u2010of\u2010function mutations and\n                      <jats:italic>PTEN<\/jats:italic>\n                      loss\u2010of\u2010function variants are associated with sustained PI3K\/AKT\/mTOR pathway activation. Integrating\n                      <jats:italic>TP53<\/jats:italic>\n                      and\n                      <jats:italic>PTEN<\/jats:italic>\n                      status with oncogenic driver profiling may facilitate the identification of biologically defined subsets and inform precision therapeutic strategies for cervical NEC.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/gcc.70173","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:53:34Z","timestamp":1789995214000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Genomic Profiling of\n                    <scp>\n                      <i>PTEN<\/i>\n                    <\/scp>\n                    and\n                    <scp>\n                      <i>TP53<\/i>\n                    <\/scp>\n                    in Cervical Neuroendocrine Carcinoma: Synergistic Roles With\n                    <scp>\n                      <i>HER2\/KRAS\/PIK3CA<\/i>\n                    <\/scp>\n                    and Implications for Precision Oncology"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6452-8221","authenticated-orcid":false,"given":"Huang\u2010Pin","family":"Shen","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Chung\u2010Shan Medical University Hospital  Taichung Taiwan"},{"name":"Department of Obstetrics and Gynecology Chung\u2010Shan Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3617-9423","authenticated-orcid":false,"given":"Ming\u2010Yung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Data Science and Big Data Analytics Providence University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8189-0751","authenticated-orcid":false,"given":"Yi\u2010Ju","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology Chung\u2010Shan Medical University Hospital  Taichung Taiwan"},{"name":"Department of Pathology Chung\u2010Shan Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3520-7066","authenticated-orcid":false,"given":"An\u2010Chi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Chung\u2010Shan Medical University Hospital  Taichung Taiwan"},{"name":"Department of Obstetrics and Gynecology Chung\u2010Shan Medical University  Taichung 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