{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T11:41:38Z","timestamp":1760960498316,"version":"build-2065373602"},"reference-count":47,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T00:00:00Z","timestamp":1760745600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Seminoma is a malignant germ cell tumor that most commonly involves the testicles but may involve the mediastinum, the retroperitoneum, and other extra-gonadal sites as well. This study aims to investigate the somatic genomic landscape of seminoma. Methods: Data for a retrospective observational analysis of seminoma was acquired from the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) with clinical and genomic data from 2017 and beyond. Using the R and R Studio software (R 4.5.0), analyses for common somatic mutations and copy number alterations were run with a statistical significance of p &lt; 0.05. Results: The most mutated genes included KIT (22.6%), KRAS (17.1%), and MTOR (5.1%), with significant copy number alterations in CDKN1B (17.2%), KRAS (14.7%), CCND2 (10.3%), and H3F3C (9.8%). These suggest involvement within the KIT\/RAS\/MAPK and PI3K\/AKT\/mTOR (PAM) pathways for seminoma development. A novel finding within comparative evaluation of PMS1 and AMER1 mutations were found in Black individuals. Additionally, our findings were consistent with a lower testicular cancer rate among individuals with African ancestry than European ancestry. BRD4 mutations were found only in metastatic samples while KMT2C, STAG2, ALK, AXL, and EGFR were only found in primary samples, suggesting a possible association. Conclusions: This study provided a comprehensive molecular and genetic profiling of seminoma including key genetic alterations, affected pathways, and potential therapeutic strategies. Moreover, overlap between pathways and gene mutations provides the potential for alternative treatment options for seminoma via multiple pathways.<\/jats:p>","DOI":"10.3390\/cancers17203363","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T10:44:10Z","timestamp":1760957050000},"page":"3363","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Characterization of Seminoma Utilizing the AACR Project GENIE: A Retrospective Observational Study"],"prefix":"10.3390","volume":"17","author":[{"given":"Suchit R.","family":"Geereddy","sequence":"first","affiliation":[{"name":"College of Biological Sciences, University of California\u2013Davis, Davis, CA 95616, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amber","family":"Chang","sequence":"additional","affiliation":[{"name":"College of Medicine, University of South Florida Health Morsani, Tampa, FL 33602, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alma","family":"Gallegos","sequence":"additional","affiliation":[{"name":"College of Biological Sciences, University of California\u2013Davis, Davis, CA 95616, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5510-7686","authenticated-orcid":false,"given":"Jonathan","family":"Lin","sequence":"additional","affiliation":[{"name":"College of Arts and Sciences, Santa Clara University, Santa Clara, CA 95053, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9693-4829","authenticated-orcid":false,"given":"Akaash","family":"Surendra","sequence":"additional","affiliation":[{"name":"Department of Medicine, Arizona State University, Tempe, AZ 85281, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suraj","family":"Puvvadi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Arizona State University, Tempe, AZ 85281, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beau","family":"Hsia","sequence":"additional","affiliation":[{"name":"School of Medicine, Creighton University, Phoenix Campus, Phoenix, AZ 85012, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abubakar","family":"Tauseef","sequence":"additional","affiliation":[{"name":"School of Medicine, Creighton University, Ohama Campus, Ohama, NE 68124, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Thirumalareddy","sequence":"additional","affiliation":[{"name":"School of Medicine, Creighton University, Ohama Campus, Ohama, NE 68124, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akshat","family":"Sood","sequence":"additional","affiliation":[{"name":"School of Medicine, Creighton University, Ohama Campus, Ohama, NE 68124, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,18]]},"reference":[{"key":"ref_1","unstructured":"Lamichhane, A., and Mukkamalla, S.K.R. 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