20.500.12556/DiRROS-23650 Melanoma antigens in pediatric medulloblastoma contribute to tumor heterogeneity and species-specificity of group 3 tumors Medulloblastoma (MB) is the most malignant childhood brain cancer. Group 3 MB (G3 MB) subtype accounts for about 25% of MB and is associated with the worst outcomes. Herein, we report that more than half of G3 MB tumors express melanoma antigens (MAGEs), which are potential prognostic and therapeutic markers. MAGEs are cancer‑testis antigens, aberrantly expressed in several adult cancers, and associated with poorer prognosis and therapy resistance; however, their role in pediatric cancers is mostly unknown. This study aimed to determine whether MAGEs are activated and important in pediatric MB. We obtained formalin‑fixed paraffin‑embedded tumor samples of 34 patients, collected between 2008 and 2015 at the Children’s Medical Center in Dallas and applied our validated reverse transcription quantitative PCR (RT‑qPCR) assay to measure the expression of 23 MAGE genes. To validate our data, we analyzed published datasets from pediatric MB tumors and patient‑derived orthotopic xenografts, totaling 949 patients. Our RT‑qPCR analysis suggested that MAGEs were expressed in G3/4MB. Further mining of bulk and single‑cell RNA‑sequencing datasets confirmed that 50–75% of G3 tumors activate several MAGEs. Intriguingly, single‑cell data analysis showed that MAGEs are expressed in distinct subsets of cells in MAGE‑positive tumors and are not activated in mouse genetic models, suggesting they contribute to the tumor heterogeneity and species‑specificity of G3 MB. We then examined how MAGE expression affects the growth and oncogenic potential by CRISPR‑Cas9‑ and siRNA‑mediated gene depletion. Depletion of MAGEAs, ‑B2, and ‑Cs altered cell survival, viability, and clonogenic growth due to decreased proliferation and increased apoptosis of MAGE‑positive MB cells. These findings suggested that targeting MAGEs could represent a viable therapeutic strategy for G3 MB. A deeper understanding of MAGE regulation and function is warranted and could aid in improving prognostic and therapeutic approaches for this poorly characterized subgroup of pediatric brain tumors. medulloblastoma tumor antigens MAGE pediatric cancer cancer‑testis antigens meduloblastom otroški možganski tumorji MAGE heterogenost terapevtske tarče true false true Angleški jezik Slovenski jezik Neznano 2025-09-19 13:56:28 2025-09-19 13:56:28 2025-10-24 03:54:45 0000-00-00 00:00:00 2025 0 0 Nasl. z nasl. zaslona; Opis vira z dne 1. 8. 2025; Soavtorji: Rebecca R. Florke Gee, Sima Tozandehjani, Tara Bayat, Maria Camila Hoyos Sanchez, Juan Sebastian Solano Gutierrez, Barbara Breznik, Anna K. Lee, Samuel T. Peters, Jon P. Connelly, Shondra M. Pruett-Miller, Martine F. Roussel, Dinesh Rakheja, Heather S. Tillman, Patrick Ryan Potts & Klementina Fon Tacer; str. 1-16 Vol. 13, [article no.] 164 2025 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2025-07-28 577.2 2051-5960 10.1186/s40478-025-02055-3 244648963 https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-025-02055-3 1 ae479916-954f-11f0-9bb7-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=35007 RAZ_Collins_Rebecca_R._J._2025.pdf RAZ_Collins_Rebecca_R._J._2025.pdf 1 DEA9F156024CEBD10AA4816873FE4C79 537f50103b4ccf32a47faf309fa33ba7439ff2383c03c50e7c92de4ab4670eed 411616d7-9551-11f0-9bb7-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=35008 Nacionalni inštitut za biologijo 0 0 0