{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T22:04:27Z","timestamp":1789596267615,"version":"build-2803163510"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T00:00:00Z","timestamp":1696377600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Spermatocytic tumor (ST) is a rare type of germ cell tumor that occurs exclusively in the postpubertal testis and typically affects elderly men. Most STs are benign, but rare cases exhibit aggressive clinical behavior, often in association with transition to sarcomatoid histology. Limited molecular analyses have been performed on STs; therefore, their genomic and epigenomic features remain incompletely described. Twenty\u2010seven samples from 25 individual patients were analyzed with a combination of DNA sequencing panels, genomic methylation profiling, SNP array, isochromosome (12p) [i(12p)] FISH, and immunohistochemistry. The series included five metastasizing tumors (three with sarcomatoid transformation, one anaplastic, and one conventional) and 20 non\u2010metastasizing tumors (14 anaplastic and six conventional). Anaplastic tumors comprised a monomorphic population of intermediate\u2010sized neoplastic cells, as previously described. Multiomic analyses demonstrated that there were two genomic subgroups of STs: one with diploid genomes and hotspot\n                    <jats:italic>RAS<\/jats:italic>\n                    \/\n                    <jats:italic>RAF<\/jats:italic>\n                    variants and the other with global ploidy shift and absence of recurrent mutations. Relative gain of chromosome 9 was a consistent finding in both subgroups. A comparison of metastasizing and non\u2010metastasizing cases demonstrated that aggressive behavior was associated with the acquisition of pathogenic\n                    <jats:italic>TP53<\/jats:italic>\n                    mutations and\/or relative gains of 12p\/i(12p). In cases with sarcomatoid transformation,\n                    <jats:italic>TP53<\/jats:italic>\n                    mutations seem to underlie the transition to sarcomatoid histology. Genomic methylation analysis demonstrated that aggressive cases with gains of 12p cluster closer to pure seminomas than to STs without gains of 12p. In conclusion, STs include two genomic subgroups, characterized by global ploidy shifts without recurrent mutations and diploid genomes with\n                    <jats:italic>RAS<\/jats:italic>\n                    \/\n                    <jats:italic>RAF<\/jats:italic>\n                    hotspot mutations, respectively. Biologic progression was associated with relative gains of 12p and\n                    <jats:italic>TP53<\/jats:italic>\n                    mutations. The findings in STs with relative gains of 12p suggest that they may exhibit biologic characteristics akin to those seen in germ cell neoplasia\n                    <jats:italic>in situ<\/jats:italic>\n                    \u2010related germ cell tumors rather than non\u2010germ cell neoplasia\n                    <jats:italic>in situ<\/jats:italic>\n                    \u2010derived STs. \u00a9 2023 The Authors.\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.6210","type":"journal-article","created":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T13:07:25Z","timestamp":1696424845000},"page":"50-60","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Genomic analysis of spermatocytic tumors demonstrates recurrent molecular alterations in cases with malignant clinical behavior"],"prefix":"10.1002","volume":"262","author":[{"given":"Sounak","family":"Gupta","sequence":"first","affiliation":[{"name":"Department of Pathology Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynette M","family":"Sholl","sequence":"additional","affiliation":[{"name":"Department of Pathology Brigham and Women's Hospital, Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiying","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathology New York University  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeboye O","family":"Osunkoya","sequence":"additional","affiliation":[{"name":"Department of Pathology Emory University School of Medicine  Atlanta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer 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Instituto Portugu\u00eas de Oncologia  Lisbon Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0752-0917","authenticated-orcid":false,"given":"Matija","family":"Snuderl","sequence":"additional","affiliation":[{"name":"Department of Pathology New York University  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle S","family":"Hirsch","sequence":"additional","affiliation":[{"name":"Department of Pathology Brigham and Women's Hospital, Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Pathology Brigham and Women's Hospital, Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross A","family":"Rowsey","sequence":"additional","affiliation":[{"name":"Department of Pathology Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael E","family":"Jimenez","sequence":"additional","affiliation":[{"name":"Department of Pathology Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C","family":"Cheville","sequence":"additional","affiliation":[{"name":"Department of Pathology Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter M","family":"Sadow","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital, Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Colecchia","sequence":"additional","affiliation":[{"name":"Department of Pathology Universita Vita Salute San Raffaele  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Costantino","family":"Ricci","sequence":"additional","affiliation":[{"name":"Pathology 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