{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T14:50:50Z","timestamp":1773067850422,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T00:00:00Z","timestamp":1772841600000},"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>Penile squamous cell carcinoma (PSCC) is rare, but a biologically aggressive malignancy. Recent comprehensive genomic profiling (CPG) efforts revealed the underlying genomic landscape of PSCC, identifying TP53, TERT, CDKN2A, PIK3CA, NOTCH1, and FAT1 as frequently altered genes with potential roles in penile oncogenesis. In addition, recurrent mutations encoded in the GPS1 gene have been observed in 7.4% of cases in a particular PSCC cohort. Functional studies demonstrated loss of function due to GPS1 Exon 9 missense mutations, proposing a possible role for these alterations as oncogenic driver events in PSCC. However, no other study confirmed the occurrence of GPS1 gene mutations in PSCC. To elucidate the biological function of GPS1 exon 9 mutations in PSCC pathogenesis, we utilized a comprehensive in-house cohort of 106 PSCC cases to explore their frequency and occurrence. Albeit, the previously reported GPS1 mutations p.D382H and p.M384I were not observed in this large cohort of PSCC cases; this analysis, however, revealed two novel GPS1 alterations in exon 9 in two (1.9%) of the analyzed cases: p.S372F (c.1115C&gt;T) and p.A375D (c.1124C&gt;A). This observation suggests that GPS1 exon 9 sequence is a target of genetic alteration during PSCC pathogenesis. However, the non-recurrent nature of these alterations indicates that they are unlikely to represent oncogenic drivers in this disease.<\/jats:p>","DOI":"10.3390\/ijms27052460","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T10:16:12Z","timestamp":1773051372000},"page":"2460","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["GPS1 Exon 9 Mutations Represent a Rare Genetic Event in Penile Squamous Cell Carcinoma Pathogenesis"],"prefix":"10.3390","volume":"27","author":[{"given":"Lars","family":"T\u00f6gel","sequence":"first","affiliation":[{"name":"Institute of Pathology, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"},{"name":"Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), 91054 Erlangen, Germany"},{"name":"Comprehensive Cancer Center Alliance WERA (CCC WERA), 91054 Erlangen, Germany"},{"name":"Bavarian Cancer Research Center (BZKF), 91054 Erlangen, Germany"},{"name":"Zentrum Personalisierte Medizin Erlangen (ZPM-Erlangen), 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9010-7668","authenticated-orcid":false,"given":"Felix","family":"Elsner","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"},{"name":"Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), 91054 Erlangen, Germany"},{"name":"Comprehensive Cancer Center Alliance WERA (CCC WERA), 91054 Erlangen, Germany"},{"name":"Bavarian Cancer Research Center (BZKF), 91054 Erlangen, 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Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernd","family":"Wullich","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), 91054 Erlangen, Germany"},{"name":"Comprehensive Cancer Center Alliance WERA (CCC WERA), 91054 Erlangen, Germany"},{"name":"Bavarian Cancer Research Center (BZKF), 91054 Erlangen, Germany"},{"name":"Zentrum Personalisierte Medizin Erlangen (ZPM-Erlangen), 91054 Erlangen, Germany"},{"name":"Department of Urology and Pediatric Urology, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0458-7075","authenticated-orcid":false,"given":"Simone","family":"Bertz","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t 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