{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T20:57:35Z","timestamp":1780952255337,"version":"3.54.1"},"reference-count":29,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"6","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Thymic epithelial tumors (TETs), which include thymomas and thymic carcinomas (TCs), are the most common neoplasms of the anterior mediastinum. To develop more effective therapeutics, it is necessary to better understand their molecular characteristics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>TET samples were profiled using next-generation sequencing (NGS) of DNA (592-gene panel or whole-exome sequencing) and RNA (whole-transcriptome sequencing). Pathogenic single nucleotide variations\/indels, deficient mismatch repair\/microsatellite instability (dMMR\/MSI) status (via immunohistochemistry and NGS), PD-L1 expression, and tumor mutational burden (TMB \u226510 mutations\/Mb) were assessed. Expression of genes encoding cell surface proteins was quantified, and pathway enrichment was evaluated using Gene Set Enrichment Analysis (GSEA). Immune cell fractions were estimated using the quanTIseq method.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Among 138 TETs, 48 (34.8%) were TCs and 90 (65.2%) thymomas.\n                      <jats:italic toggle=\"yes\">TP53<\/jats:italic>\n                      was the most frequently mutated gene, followed by\n                      <jats:italic toggle=\"yes\">KIT<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">CDKN2A<\/jats:italic>\n                      . Alterations in cell cycle (13.8%), DNA repair (8.0%), and chromatin remodeling (19.6%) genes were more common in TCs. Deletions in\n                      <jats:italic toggle=\"yes\">CDKN2A<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">CDKN2B<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">MTAP<\/jats:italic>\n                      were significantly enriched in TCs. dMMR\/MSI-H was observed in five cases, primarily TCs, and correlated with TMB-H in 80% of these. GSEA showed enrichment of\n                      <jats:italic toggle=\"yes\">MYC<\/jats:italic>\n                      , angiogenesis, epithelial-mesenchymal transition, and mTORC1 pathways in TCs.\n                      <jats:italic toggle=\"yes\">ERBB2<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">ERBB3<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">TACSTD2<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">NECTIN4<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">MSLN<\/jats:italic>\n                      were overexpressed in TCs, while\n                      <jats:italic toggle=\"yes\">EGFR<\/jats:italic>\n                      was more highly expressed in thymomas. TETs exhibited high PD-L1 expression, low TMB, and subtype-specific immune profiles.\n                      <jats:italic toggle=\"yes\">TP53<\/jats:italic>\n                      mutations were significantly associated with worse survival.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Integrated profiling of TETs reveals distinct genomic, transcriptomic, and immune features across subtypes of TETs and identifies potentially actionable therapeutic targets that may inform future treatment strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po-26-00001","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T20:00:12Z","timestamp":1780948812000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Molecular and Clinical Analysis of Thymic 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