{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:19:00Z","timestamp":1785410340084,"version":"3.56.0"},"reference-count":61,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T00:00:00Z","timestamp":1782518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006315","name":"Shanfield Family and CureSearch for Children\u2019s Cancer","doi-asserted-by":"publisher","award":["685676"],"award-info":[{"award-number":["685676"]}],"id":[{"id":"10.13039\/100006315","id-type":"DOI","asserted-by":"publisher"}]},{"award":["685676"],"award-info":[{"award-number":["685676"]}],"id":[{"id":"https:\/\/ror.org\/01521js97","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Germ cell tumors (GCTs) are thought to arise from primordial germ cells that fail to appropriately differentiate and instead retain pluripotency programs. PRDM14 is a key regulator of pluripotency and primordial germ cell specification and is aberrantly expressed in multiple GCT subtypes. However, the role of PRDM14 in GCT malignancy remains unclear. In this study, we investigated whether PRDM14 functions in GCTs through CBFA2T2, a transcriptional corepressor previously identified as a PRDM14-interacting partner in pluripotent stem cells and developmental models. Methods: To determine the presence and level of PRDM14 and CBFA2T2 in GCT, a panel of GCT lines were assessed for RNA and protein expression and interaction. Then, to better understand the biological effects of PRDM14 and CBFA2T2 within GCTs, PRDM14 and CBFA2T2 knockdowns were employed. Results: We show that PRDM14 and CBFA2T2 are expressed across GCT cell lines, colocalize predominantly in the nucleus, and cooperate as a complex in GCT cell lines. Knockdown of either PRDM14 or CBFA2T2 resulted in reduced expression of key pluripotency genes and a significant impairment of cell proliferation, indicating a shared role in maintaining an undifferentiated, proliferative state. Transcriptomic analysis following PRDM14 or CBFA2T2 depletion revealed extensive overlap in differentially expressed genes and convergent alterations in developmental and metabolic signaling pathways. Conclusions: Together, these findings suggest that PRDM14 and CBFA2T2 form a functional complex that sustains pluripotency and proliferation in GCT cells. This supports a model in which persistence of germline regulatory mechanisms contributes to GCT malignancy, highlighting this interaction as a novel component of GCT biology.<\/jats:p>","DOI":"10.3390\/cancers18132090","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T02:16:44Z","timestamp":1782699404000},"page":"2090","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Interaction Between PRDM14 and CBFA2T2 Supports Pluripotency and Proliferation in Germ Cell Tumors"],"prefix":"10.3390","volume":"18","author":[{"given":"Deana Leah","family":"Wood","sequence":"first","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2544-5888","authenticated-orcid":false,"given":"Aaron Michael","family":"Taylor","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jody Therieault","family":"Lombardi","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0364-7443","authenticated-orcid":false,"given":"Patrick Kwok Shing","family":"Ng","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA"},{"name":"Department of Pediatrics, School of Medicine, University of Connecticut, Farmington, CT 06032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9173-8366","authenticated-orcid":false,"given":"Ching C.","family":"Lau","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA"},{"name":"Department of Pediatrics, School of Medicine, University of Connecticut, Farmington, CT 06032, USA"},{"name":"Center for Cancer and Blood Disorders, Connecticut Children\u2019s, Hartford, CT 06106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1176-8272","authenticated-orcid":false,"given":"Joanna J.","family":"Gell","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA"},{"name":"Department of Pediatrics, School of Medicine, University of Connecticut, Farmington, CT 06032, USA"},{"name":"Center for Cancer and Blood Disorders, Connecticut Children\u2019s, Hartford, CT 06106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1200\/JCO.23.01099","article-title":"Adolescent and Young Adult Germ Cell Tumors: Epidemiology, Genomics, Treatment, and Survivorship","volume":"42","author":"Travis","year":"2024","journal-title":"J. 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