{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T09:07:42Z","timestamp":1778836062388,"version":"3.51.4"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T00:00:00Z","timestamp":1773446400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T00:00:00Z","timestamp":1773446400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Malignant germ cell tumors (GCTs) are relatively rare tumors with limited therapeutic options. This study examined the homologous recombination deficiency (HRD) status and genomic characteristics in 14 patients with GCT who underwent next\u2010generation sequencing. HRD was evaluated using the genomic instability score (GIS), which incorporates three components: loss of heterozygosity (LOH), telomeric allelic imbalance (TAI), and large\u2010scale transition (LST). Our findings showed that 57.1% (8\/14) of participants were HRD positive. Female patients presented a significantly higher prevalence of HRD positivity (87.5%, 7\/8) compared with male patients (16.7%, 1\/6). HRD positivity in female cases had a mean GIS of 56 (range 48\u201376), including one patient harboring a germline\n                    <jats:italic>BRCA2<\/jats:italic>\n                    p.S2670L (c.8009C&gt;T) likely pathogenic mutation. LST demonstrated the strongest correlation with the integrated GIS (\n                    <jats:italic>R<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u20090.945), followed by LOH (\n                    <jats:italic>R<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u20090.872). Distinct mutation patterns were observed based on gender. GCTs in male cases predominantly exhibited mutations in\n                    <jats:italic>TP53<\/jats:italic>\n                    (50% in yolk sac tumors; 50% in teratomas). GCTs in male cases also demonstrated\n                    <jats:italic>TP53<\/jats:italic>\n                    mutations in one mediastinal yolk sac tumor and one mediastinal teratoma. Male cases showed recurrent alterations in\n                    <jats:italic>KRAS<\/jats:italic>\n                    ,\n                    <jats:italic>PRKDC<\/jats:italic>\n                    , and\n                    <jats:italic>CDKN1B<\/jats:italic>\n                    , alongside frequent chromosome 12p amplifications in two cases. One particularly complex mediastinal teratoma in a male patient, featuring rhabdomyosarcomatous transformation, displayed bidirectional intergenic (\n                    <jats:italic>TWSG1, MANEA\u2010DT<\/jats:italic>\n                    )\u2010ROS1fusions, a\n                    <jats:italic>HRAS<\/jats:italic>\n                    \u2010intergenic (\n                    <jats:italic>RNH1<\/jats:italic>\n                    ) fusion, and\n                    <jats:italic>MET<\/jats:italic>\n                    focal amplification. These findings suggest a promising therapeutic opportunity with poly (ADP\u2010ribose) polymerase (PARP) inhibitors for female patients with HRD\u2010positive GCTs. Additionally, the complex composition of gene variants found in male patients with GCTs, including\n                    <jats:italic>ROS1<\/jats:italic>\n                    fusions and\n                    <jats:italic>MET<\/jats:italic>\n                    focal amplification, points toward potential targeted therapeutic strategies. This study underscores the presence of sex\u2010specific therapeutic vulnerabilities in GCTs, which warrant further exploration in larger cohorts. \u00a9 2026 The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.70047","type":"journal-article","created":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T16:05:29Z","timestamp":1773504329000},"page":"210-221","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genomic landscape and homologous recombination deficiency in malignant germ cell tumors reveals sex\u2010specific therapeutic opportunities"],"prefix":"10.1002","volume":"269","author":[{"given":"Boheng","family":"Xu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat\u2010sen University Cancer Center  Guangzhou PR China"},{"name":"Department of Molecular 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