{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T16:28:45Z","timestamp":1789576125985,"version":"build-2803163510"},"reference-count":43,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Molecular profiling of testicular germ cell tumors (TGCTs) provides critical insights into personalized treatment approaches, particularly for patients with recurrent or treatment-resistant disease. In this study, we retrospectively analyzed clinicopathological and targeted genomic sequencing data from 27 TGCT patients, including 7 seminomas, 19 non-seminomas, and 1 prepubertal type teratoma, across stage I (48%), stage II (41%), and stage III (11%). Tumor samples were obtained from 27 orchiectomies, with additional pathological specimens collected from 16 of these patients during retroperitoneal lymph node dissections (RPLNDs); these included 8 chemotherapy-na\u00efve and 8 post-chemotherapy cases. The median tumor mutational burden (TMB) was 0.5 mutations\/Mb, consistent with the low mutation rate typically observed in TGCTs. Somatic mutations and copy number gain alterations were detected in 56% (15\/27) of patients, primarily in KRAS (25.9%), KIT (11.1%), and PIK3CB (7.4%). PD-L1 positive immunoreactivity by immunohistochemistry was observed in 75% of tumors (60% in stage I, 100% in stage III) analyzed (n = 8), suggesting potential immune checkpoint inhibitor applicability in advanced disease. Microsatellite instability (MSI) status was identified in 23 tumors; all were classified as MSI-low, supporting the rarity of MSI-driven tumorigenesis in TGCTs. Actionable gene alterations linked to FDA-approved therapies, interventional therapies, and clinical trials in TGCTs and other cancers (lung, skin, colon, liver, stomach, and breast) were present in 59.3% (16\/27) of patients, indicating potential therapeutic repurposing. Additionally, germline variants of uncertain clinical significance in known cancer actionable genes, including MSH2, MSH6, RB1, and BRCA2, were found in 9 patients, warranting further investigation regarding their clinical relevance and susceptibility risk. Our findings highlight that a substantial proportion of TGCT patients harbor potentially actionable molecular alterations across all disease stages.<\/jats:p>","DOI":"10.3390\/ijms26188963","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T08:56:46Z","timestamp":1758013006000},"page":"8963","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Molecular Features and Actionable Gene Targets of Testicular Germ Cell Tumors in a Real-World Setting"],"prefix":"10.3390","volume":"26","author":[{"given":"Rafael","family":"Morales-Grimany","sequence":"first","affiliation":[{"name":"Department of Medicine, School of Medicine, Universidad Central del Caribe, Bayamon, PR 00956, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krinio","family":"Giannikou","sequence":"additional","affiliation":[{"name":"Department of Urology, Moores Cancer Center, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesar","family":"Delgado","sequence":"additional","affiliation":[{"name":"Department of Urology, Moores Cancer Center, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kshitij","family":"Pandit","sequence":"additional","affiliation":[{"name":"Department of Urology, Moores Cancer Center, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fady","family":"Baky","sequence":"additional","affiliation":[{"name":"Department of Urology, School of Medicine, University of Texas Southwestern, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armon","family":"Amini","sequence":"additional","affiliation":[{"name":"Department of Urology, School of Medicine, University of Texas Southwestern, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kit","family":"Yuen","sequence":"additional","affiliation":[{"name":"Department of Urology, Moores Cancer Center, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8877-6799","authenticated-orcid":false,"given":"Thomas","family":"Gerald","sequence":"additional","affiliation":[{"name":"Department of Urology, School of Medicine, University of Texas Southwestern, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6134-1237","authenticated-orcid":false,"given":"Rohit","family":"Badia","sequence":"additional","affiliation":[{"name":"Department of Urology, School of Medicine, University of Texas Southwestern, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Urology, School of Medicine, University of Texas Southwestern, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology, Moores Cancer Center, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Javier-Desloges","sequence":"additional","affiliation":[{"name":"Department of Urology, Moores Cancer Center, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitaly","family":"Margulis","sequence":"additional","affiliation":[{"name":"Department of Urology, School of Medicine, University of Texas Southwestern, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solomon","family":"Woldu","sequence":"additional","affiliation":[{"name":"Department of Urology, School of Medicine, University of Texas Southwestern, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amirali","family":"Salmasi","sequence":"additional","affiliation":[{"name":"Department of Urology, Moores Cancer Center, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred","family":"Millard","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rana R.","family":"Mckay","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3358-1193","authenticated-orcid":false,"given":"Aditya","family":"Bagrodia","sequence":"additional","affiliation":[{"name":"Department of Urology, Moores Cancer Center, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA"},{"name":"Department of Urology, School of Medicine, University of Texas Southwestern, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,15]]},"reference":[{"key":"ref_1","unstructured":"(2025, April 10). 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