{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T15:37:24Z","timestamp":1770824244630,"version":"3.50.1"},"reference-count":75,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T00:00:00Z","timestamp":1684454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Isochromosome 12p (iChr12p) is typical in almost all invasive testicular cancers. Increased copy number of genes on 12p is associated with the development of a clinically manifest tumor; however, the causative genes have not yet been identified. Chromosome 12 harbors many genes involved in Vitamin D metabolism. RNAseq analysis of Vitamin D receptor (VDR) genes from the TCGA cohort revealed that clustering of VDR expression signatures could differentiate between pure seminomas and non-seminomatous germ cell tumors (NSGCT). Using TCGA mRNA expression of anabolic (CYP2R1, CYP27A1 and CYP27B1) and catabolic (CYP24A1) Vitamin D enzymes, positive (PTHLH, IFNG, and TNF) and negative (FGF23) feedback regulators could also clearly distinguish between pure seminomas and NSGCT. We hypothesize that the regulation of Vitamin D metabolism might be disturbed through iChr12p formation, influencing testicular carcinogenesis via increased FGF23 and PTHLH expression. While FGF23 represses CYP27B1 and activates catabolism of active hormone, increased PTHLH secretion can lead to hypercalcemia via inactivation of VDR. In conclusion, testicular cancer is associated with extensive modifications in intratesticular Vitamin D homeostasis. Further research is needed to clarify whether Vitamin D deficiency causes the formation of iChr12p and whether Vitamin D deficiency via iChr12p genomic aberration is involved in testicular carcinogenesis.<\/jats:p>","DOI":"10.3390\/nu15102384","type":"journal-article","created":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T09:23:10Z","timestamp":1684488190000},"page":"2384","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Isochromosome 12p Formation Regulates Vitamin D Metabolism in Testicular Cancer"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0661-388X","authenticated-orcid":false,"given":"Peter","family":"T\u00f6rzs\u00f6k","sequence":"first","affiliation":[{"name":"Department of Urology and Andrology, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jasper","family":"Van Goubergen","sequence":"additional","affiliation":[{"name":"Division of Experimental Urology, Department of Urology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8701-9462","authenticated-orcid":false,"given":"Martin","family":"Pichler","sequence":"additional","affiliation":[{"name":"Division of Oncology, Department of Internal Medicine, Medical University of Graz, 8010 Graz, Austria"},{"name":"Translational Oncology, University Hospital of Augsburg, 86156 Augsburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5286-9048","authenticated-orcid":false,"given":"Renate","family":"Pichler","sequence":"additional","affiliation":[{"name":"Department of Urology, Comprehensive Cancer Center Innsbruck, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4591-6368","authenticated-orcid":false,"given":"Fr\u00e9d\u00e9ric R.","family":"Santer","sequence":"additional","affiliation":[{"name":"Division of Experimental Urology, Department of Urology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e12390","DOI":"10.1097\/MD.0000000000012390","article-title":"Recent Global Trends in Testicular Cancer Incidence and Mortality","volume":"97","author":"Park","year":"2018","journal-title":"Medicine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1016\/j.fertnstert.2020.04.042","article-title":"Association between Male Infertility and Male-Specific Malignancies: Systematic Review and Meta-Analysis of Population-Based Retrospective Cohort Studies","volume":"114","author":"Kasman","year":"2020","journal-title":"Fertil. 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