Medulloblastoma’s master regulators and their association with patients’ risk

Medulloblastoma’s master regulators and their association with patients’ risk

Abstract Medulloblastoma (MB) is the most common malignant pediatric brain tumor, accounting for approximately 20% of all childhood brain tumors. Despite recent advances, current treatments like surgery, radiation, and chemotherapy still lead to severe side effects and high morbidity. Limited knowle...

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Main Authors: Gustavo Lovatto Michaelsen, Tayrone de Sousa Monteiro, Danilo Oliveira Imparato, João Vitor Almeida da Costa, Daniel Rocha Silva, Iara Dantas de Souza, Marcel Câmara da Ribeiro-Dantas, Otávio Cabral-Marques, Marialva Sinigaglia, Rodrigo Juliani Siqueira Dalmolin
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Scientific Reports
Subjects:
Medulloblastoma
Transcription factor
Regulome
Systems biology
Online Access:https://doi.org/10.1038/s41598-025-00763-3
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Summary:Abstract Medulloblastoma (MB) is the most common malignant pediatric brain tumor, accounting for approximately 20% of all childhood brain tumors. Despite recent advances, current treatments like surgery, radiation, and chemotherapy still lead to severe side effects and high morbidity. Limited knowledge exists regarding the regulatory mechanisms behind the MB transcriptional alterations in high-aggressive subgroups like Group 3 and Group 4, hindering the development of targeted therapies. Identifying key transcriptional regulators, known as master regulators (MRs), can elucidate the dysregulated pathways underlying MB progression and uncover potential treatment targets. In this study, we utilize primary MB gene expression samples to infer its regulatory network. Subsequently, we applied the Master Regulator Analysis identifying the transcription factors BHLHE41, RFX4, and NPAS3 as its main transcriptional regulators, showing tumor suppressor features. We also identified eight risk MRs highly associated with patient outcome: four regulators (MYC, REL, ZSCAN5 A, and ZFAT) with activities associated with poor prognosis, and four (PAX6, ARNT2, ZNF157, and HIVEP3) acting antagonistically, being associated with good outcome. Our results offer key insights into the molecular mechanisms driving these tumors and identify novel potential therapeutic targets, addressing the urgent need for more effective and less toxic treatments.
ISSN:2045-2322

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