biostudies-literatureBorgenvik AVetenskapsrådetCancer Research UKAction Medical ResearchSvenska LäkaresällskapetBarncancerfondenCancerfondenRagnar Söderbergs stiftelseScience for Life LaboratoryÅke Wiberg StiftelseEuropean Research CouncilWorldwide Cancer ResearchMedical Research CouncilNational Institute for Health Research (NIHR)NCI NIH HHS4586-4603https://www.ebi.ac.uk/biostudies/studies/S-EPMC9755969biostudies-literatureUnknown82(24)Relapse is the leading cause of death in patients with medulloblastoma, the most common malignant pediatric brain tumor. A better understanding of the mechanisms underlying recurrence could lead to more effective therapies for targeting tumor relapses. Here, we observed that SOX9, a transcription factor and stem cell/glial fate marker, is limited to rare, quiescent cells in high-risk medulloblastoma with MYC amplification. In paired primary-recurrent patient samples, SOX9-positive cells accumulated in medulloblastoma relapses. SOX9 expression anti-correlated with MYC expression in murine and human medulloblastoma cells. However, SOX9-positive cells were plastic and could give rise to a MYC high state. To follow relapse at the single-cell level, an inducible dual Tet model of medulloblastomCancer researchDormant SOX9-Positive Cells Facilitate MYC-Driven Recurrence of Medulloblastoma.PMC9755969233911796640275CL-2014-01-502MR/V001647/1P30 CA030199Bravo MBWenz ASWechsler-Reya RJKalushkova AGarancher AHill RMRemke MCancer MGiraud GZhao MBorgenvik ASundstrom AClifford SCVerbaan ADRusert JMChen XDang YBolin SHutter SRahmanto ASTaylor MDSattanino DRichardson SOlsen TKSwartling FJRosen GSangfelt OMainwaring OJWeishaupt HDubuc AMBergstrom TJernberg-Wiklund HSchuller UFotaki GSavov VHolmberg KOfalseDormant SOX9-Positive Cells Facilitate MYC-Driven Recurrence of Medulloblastoma.Relapse is the leading cause of death in patients with medulloblastoma, the most common malignant pediatric brain tumor. A better understanding of the mechanisms underlying recurrence could lead to more effective therapies for targeting tumor relapses. Here, we observed that SOX9, a transcription factor and stem cell/glial fate marker, is limited to rare, quiescent cells in high-risk medulloblastoma with MYC amplification. In paired primary-recurrent patient samples, SOX9-positive cells accumulated in medulloblastoma relapses. SOX9 expression anti-correlated with MYC expression in murine and human medulloblastoma cells. However, SOX9-positive cells were plastic and could give rise to a MYC high state. To follow relapse at the single-cell level, an inducible dual Tet model of medulloblastom2022-01-01T00:00:00Z2022 Dec2026-05-28T03:43:00.563Z2025-04-04T20:22:20.404ZS-EPMC97559693621939810.1158/0008-5472.CAN-22-2108