{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T06:47:46Z","timestamp":1776494866561,"version":"3.51.2"},"reference-count":43,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,9,17]],"date-time":"2019-09-17T00:00:00Z","timestamp":1568678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FCT - Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["POCI-01-0145-FEDER-29043"],"award-info":[{"award-number":["POCI-01-0145-FEDER-29043"]}]},{"name":"FCT - Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["SFRH\/BD\/132751\/2017"],"award-info":[{"award-number":["SFRH\/BD\/132751\/2017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: The event of X chromosome inactivation induced by XIST, which is physiologically observed in females, is retained in testicular germ cell tumors (TGCTs), as a result of a supernumerary X chromosome constitution. X chromosome inactivation also occurs in male germline, specifically during spermatogenesis. We aimed to analyze the promoter methylation status of XIST in a series of TGCT tissues, representative cell lines, and testicular parenchyma. Methods: Two independent cohorts were included, comprising a total of 413 TGCT samples, four (T)GCT cell lines, and 86 testicular parenchyma samples. The relative amount of methylated and demethylated XIST promoter fragments was assessed by quantitative methylation-specific PCR (qMSP) and more sensitive high-resolution melting (HRM) methylation analyses. Results: Seminomas showed a lower amount of methylated XIST fragments as compared to non-seminomas or normal testis (p &lt; 0.0001), allowing for a good discrimination among these groups (area under the curve 0.83 and 0.81, respectively). Seminomas showed a significantly higher content of demethylated XIST as compared to non-seminomas. The percentage of demethylated XIST fragment in cell lines reflected their chromosomal constitution (number of extra X chromosomes). A novel and strong positive correlation between the Johnsen\u2019s score and XIST demethylation was identified (r = 0.75, p &lt; 0.0001). Conclusions: The X chromosome inactivation event and demethylated XIST promoter are promising biomarkers for TGCTs and for assessing spermatogenesis quality.<\/jats:p>","DOI":"10.3390\/cancers11091385","type":"journal-article","created":{"date-parts":[[2019,9,23]],"date-time":"2019-09-23T04:50:21Z","timestamp":1569214221000},"page":"1385","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["XIST-Promoter Demethylation as Tissue Biomarker for Testicular Germ Cell Tumors and Spermatogenesis Quality"],"prefix":"10.3390","volume":"11","author":[{"given":"Jo\u00e3o","family":"Lobo","sequence":"first","affiliation":[{"name":"Princess Ma\u0301xima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands"},{"name":"Department of Pathology, Portuguese Oncology Institute of Porto (IPOP), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Cancer Biology and Epigenetics Group, Research Center of Portuguese Oncology Institute of Porto (GEBC CI-IPOP) and Porto Comprehensive Cancer Center (P.CCC), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-513 Porto, Portugal"}]},{"given":"Sandra P.","family":"Nunes","sequence":"additional","affiliation":[{"name":"Cancer Biology and Epigenetics Group, Research Center of Portuguese Oncology Institute of Porto (GEBC CI-IPOP) and Porto Comprehensive Cancer Center (P.CCC), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"given":"Ad J. M.","family":"Gillis","sequence":"additional","affiliation":[{"name":"Princess Ma\u0301xima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands"}]},{"given":"Daniela","family":"Barros-Silva","sequence":"additional","affiliation":[{"name":"Cancer Biology and Epigenetics Group, Research Center of Portuguese Oncology Institute of Porto (GEBC CI-IPOP) and Porto Comprehensive Cancer Center (P.CCC), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"given":"Vera","family":"Miranda-Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Cancer Biology and Epigenetics Group, Research Center of Portuguese Oncology Institute of Porto (GEBC CI-IPOP) and Porto Comprehensive Cancer Center (P.CCC), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"given":"Annette van den","family":"Berg","sequence":"additional","affiliation":[{"name":"Princess Ma\u0301xima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands"}]},{"given":"Mariana","family":"Cantante","sequence":"additional","affiliation":[{"name":"Department of Pathology, Portuguese Oncology Institute of Porto (IPOP), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Cancer Biology and Epigenetics Group, Research Center of Portuguese Oncology Institute of Porto (GEBC CI-IPOP) and Porto Comprehensive Cancer Center (P.CCC), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"given":"Rita","family":"Guimar\u00e3es","sequence":"additional","affiliation":[{"name":"Department of Pathology, Portuguese Oncology Institute of Porto (IPOP), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Cancer Biology and Epigenetics Group, Research Center of Portuguese Oncology Institute of Porto (GEBC CI-IPOP) and Porto Comprehensive Cancer Center (P.CCC), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"given":"Rui","family":"Henrique","sequence":"additional","affiliation":[{"name":"Department of Pathology, Portuguese Oncology Institute of Porto (IPOP), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Cancer Biology and Epigenetics Group, Research Center of Portuguese Oncology Institute of Porto (GEBC CI-IPOP) and Porto Comprehensive Cancer Center (P.CCC), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-513 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4186-5345","authenticated-orcid":false,"given":"Carmen","family":"Jer\u00f3nimo","sequence":"additional","affiliation":[{"name":"Cancer Biology and Epigenetics Group, Research Center of Portuguese Oncology Institute of Porto (GEBC CI-IPOP) and Porto Comprehensive Cancer Center (P.CCC), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-513 Porto, Portugal"}]},{"given":"Leendert H. J.","family":"Looijenga","sequence":"additional","affiliation":[{"name":"Princess Ma\u0301xima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands"},{"name":"Department of Pathology, Lab. for Exp. Patho-Oncology (LEPO), Erasmus MC-University Medical Center Rotterdam, Cancer Institute, Be-432A, PO Box 2040, 3000 CA Rotterdam, The Netherlands"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lobo, J., Gillis, A.J.M., Jeronimo, C., Henrique, R., and Looijenga, L.H.J. (2019). Human Germ Cell Tumors are Developmental Cancers: Impact of Epigenetics on Pathobiology and Clinic. Int. J. Mol. 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