biostudies-literaturede Sousa GRNCATS NIH HHSNCI NIH HHSNIH HHS1597-1610https://www.ebi.ac.uk/biostudies/studies/S-EPMC12309711biostudies-literatureUnknown27(6)<h4>Background</h4>Posterior fossa molecular subtype A (PFA) ependymoma occurs in young children and is the deadliest subtype of pediatric ependymoma. High-risk subtypes with chromosome 1q + and/or 6q- exhibit significantly poorer outcomes compared to wild-type PFA. However, 50% of wild-type PFA patients relapse and there is a high risk of gaining chromosome 1q at recurrence. We previously found constitutively active NF-κB, through loss of LDOC1, led to chronic IL-6 secretion and an overall immunosuppressive tumor microenvironment in the higher-risk wild-type PFA ependymoma subset (PFA1).<h4>Methods</h4>In this study, we delineate the mechanistic consequences of LDOC1 loss in PFA1, using our PFA ependymoma in vitro and in vivo models under normoxia and hypoxia conditions.<h4>Results</h4>WeNeuro-oncologyLoss of LDOC1 by chromatin compaction in mesenchymal tumor cells is required for PFA1 ependymoma growth.PMC12309711P30 CA046934S10 OD023485R01 CA239302UM1 TR004399Valera ETPhang TLevy JMMJones KMDahl NAGrimaldo ESobral LMLiu TGriesinger AMCalzadilla AJHandler MDonson AMVibhakar Rde Sousa GRAmani VForeman NKHankinson TVenkataraman SfalseLoss of LDOC1 by chromatin compaction in mesenchymal tumor cells is required for PFA1 ependymoma growth.<h4>Background</h4>Posterior fossa molecular subtype A (PFA) ependymoma occurs in young children and is the deadliest subtype of pediatric ependymoma. High-risk subtypes with chromosome 1q + and/or 6q- exhibit significantly poorer outcomes compared to wild-type PFA. However, 50% of wild-type PFA patients relapse and there is a high risk of gaining chromosome 1q at recurrence. We previously found constitutively active NF-κB, through loss of LDOC1, led to chronic IL-6 secretion and an overall immunosuppressive tumor microenvironment in the higher-risk wild-type PFA ependymoma subset (PFA1).<h4>Methods</h4>In this study, we delineate the mechanistic consequences of LDOC1 loss in PFA1, using our PFA ependymoma in vitro and in vivo models under normoxia and hypoxia conditions.<h4>Results</h4>We2025-01-01T00:00:00Z2025 Jul2026-03-16T05:53:28.471Z2025-08-14T03:06:23.763ZS-EPMC123097113990172310.1093/neuonc/noaf029