{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T08:27:42Z","timestamp":1786523262087,"version":"build-2736575974"},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":223,"URL":"https:\/\/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"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pediatric testicular and ovarian germ cell tumors generally have favorable outcomes, but a subset of patients experience relapse, progression, or persistent disease. Conventional risk assessment is based primarily on stage, histology, primary site, serum tumor markers, and treatment response; the incremental prognostic value of genomic profiling remains uncertain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This retrospective molecular clinicopathological study included 72 patients younger than 18 years with primary testicular or ovarian germ cell tumors diagnosed from January 2014 to December 2023. Pretreatment formalin\u2010fixed paraffin\u2010embedded (FFPE) tumor specimens underwent targeted next\u2010generation sequencing with a custom 89\u2010gene hybrid\u2010capture panel. One qualifying feature was counted for each pathogenic or likely pathogenic\n                      <jats:italic>TP53<\/jats:italic>\n                      mutation, chromosome 12p gain,\n                      <jats:italic>KRAS<\/jats:italic>\n                      amplification, and each additional pathogenic or likely pathogenic oncogenic alteration retained after annotation; tumors with two or more qualifying features were classified as signature\u2010positive. Event\u2010free survival (EFS) was the primary endpoint, and overall survival (OS) was secondary.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The cohort comprised 45 ovarian and 27 testicular tumors. Recurrent alterations included chromosome 12p gain;\n                      <jats:italic>KRAS<\/jats:italic>\n                      ,\n                      <jats:italic>TP53<\/jats:italic>\n                      ,\n                      <jats:italic>KIT<\/jats:italic>\n                      , and\n                      <jats:italic>NRAS<\/jats:italic>\n                      mutations; and\n                      <jats:italic>KRAS<\/jats:italic>\n                      amplification. Twenty tumors were signature\u2010positive, and 52 were signature\u2010negative. Events occurred in 35.0% versus 17.3%, and 3\u2010year EFS was 65.0% versus 88.5% (log\u2010rank\n                      <jats:italic>p<\/jats:italic>\n                      = 0.019). The stage\u2010adjusted hazard ratio for EFS was 2.74 (95% confidence interval, 1.01\u20137.43;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.048). Three\u2010year OS was 85.0% versus 98.1% and did not differ significantly (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.087).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Targeted sequencing identified recurrent mutations and copy\u2010number alterations in pediatric gonadal germ cell tumors. The exploratory adverse genomic signature was associated with EFS but not OS. This hypothesis\u2010generating finding requires independent validation and does not establish mandatory testing, treatment escalation, or modification of first\u2010line therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/humu\/3009537","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T07:34:41Z","timestamp":1786520081000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Mutation Profiling and Prognostic Genomic Signature in Pediatric Testicular and Ovarian Germ Cell 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