{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:30Z","timestamp":1787028570335,"version":"build-2736575974"},"reference-count":47,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cancer Research Center of Tehran University of Medical Science","award":["99-1-115-47842"],"award-info":[{"award-number":["99-1-115-47842"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Transition is an essential mechanism that drives the development of distinct cellular phenotypes and tumorigenesis. The expression of various types of testis cancer antigens (TCAs) in breast carcinomas suggests a potential transition to male germ cell features within the tumor. This study explores the cellular populations in breast cancer that express genes associated with male germ cell development. We re-analyzed published datasets to identify the germline-associated genes in breast tumors. We then experimentally validated the expression of the identified genes in 28 breast tissue tumor samples using a quantitative RT-PCR. Based on available datasets, we also performed single-cell RNA sequencing (scRNA-seq) to analyze the tumor heterogeneity and cellular clustering. A total of 455 overexpressed genes were identified that were related to fetal primordial germ cells (PGCs), particularly those in the male gonad. Our examinations showed a significant overexpression of five genes (CCNB1, CCNB2, PTTG1, RACGAP1, and UBE2C) in the tumor samples. The scRNA-seq analysis revealed 14 distinct cell clusters, characterized by different gene expression signatures and cell cycle phases. The breast tumor stromal cells were suggested as the main source of the germline-associated genes. This study provides insights into the molecular mechanisms and pathways involved in germ cell transition in breast carcinoma.<\/jats:p>","DOI":"10.3390\/ijms26188958","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T08:56:46Z","timestamp":1758013006000},"page":"8958","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Investigating Germ Cell Transition Genes in Breast Cancer: Exploring the Genesis of Cancer Testis-Associated Markers"],"prefix":"10.3390","volume":"26","author":[{"given":"Hamid","family":"Khodayari","sequence":"first","affiliation":[{"name":"Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran 1419733141, Iran"},{"name":"International Center for Personalized Medicine (P7MEDICINE), Luise-Rainer-Str. 6-12, 40235 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeed","family":"Khodayari","sequence":"additional","affiliation":[{"name":"Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran 1419733141, Iran"},{"name":"International Center for Personalized Medicine (P7MEDICINE), Luise-Rainer-Str. 6-12, 40235 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4832-7980","authenticated-orcid":false,"given":"Mohammad","family":"Dashtkoohi","sequence":"additional","affiliation":[{"name":"Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran 1419733141, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amirnader Emami","family":"Razavi","sequence":"additional","affiliation":[{"name":"Iran National Tumor Bank, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran 1419733141, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyed Rouhollah","family":"Miri","sequence":"additional","affiliation":[{"name":"Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran 1419733141, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahad","family":"Mohamadnejad","sequence":"additional","affiliation":[{"name":"Cancer Biology Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran 1419733141, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo de Castro","family":"Santos","sequence":"additional","affiliation":[{"name":"Sanacare Gruppenpraxis Rue du Marche-Neuf 27, 2503 Bienne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1850-6402","authenticated-orcid":false,"given":"Fabio","family":"Comuzzi","sequence":"additional","affiliation":[{"name":"Hospital Du Jura, Faubourg Capucin 30, 2800 Del\u00e9mont, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Shirkoohi","sequence":"additional","affiliation":[{"name":"Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran 1419733141, Iran"},{"name":"Cancer Biology Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran 1419733141, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Habibollah","family":"Mahmoodzadeh","sequence":"additional","affiliation":[{"name":"Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran 1419733141, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karim","family":"Nayernia","sequence":"additional","affiliation":[{"name":"International Center for Personalized Medicine (P7MEDICINE), Luise-Rainer-Str. 6-12, 40235 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,15]]},"reference":[{"key":"ref_1","first-page":"394","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. 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