{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T07:36:59Z","timestamp":1772523419015,"version":"3.50.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T00:00:00Z","timestamp":1738627200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>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\u2005+\u2005and\/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-\u03baB, 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).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We noted chromatin compaction by H3K27me3 at the LDOC1 loci results in loss of LDOC1 gene expression. Restoration of LDOC1 was sufficient to reduce proliferation, NF-\u03baB signaling, and a significant decrease in IL-6 secretion. Furthermore, tumors implanted with LDOC1-transduced cells in vivo were out competed by non-transduced cells, suggesting loss of LDOC1 is required for PFA tumor growth.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>These findings shed further light on the biology of PFA1 ependymoma and the role LDOC1 loss has on the tumor and immunobiology of high-risk pediatric ependymoma.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/neuonc\/noaf029","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T02:51:36Z","timestamp":1738637496000},"page":"1597-1610","source":"Crossref","is-referenced-by-count":1,"title":["Loss of LDOC1 by chromatin compaction in mesenchymal tumor cells is required for PFA1 ependymoma growth"],"prefix":"10.1093","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1809-8539","authenticated-orcid":false,"given":"Graziella Ribeiro","family":"de Sousa","sequence":"first","affiliation":[{"name":"Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo , Ribeir\u00e3o Preto ,","place":["Brazil"]},{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus , Aurora, Colorado ,","place":["USA"]},{"name":"Morgan Adams Foundation Pediatric Brain Tumor Research Program, Children\u2019s Hospital Colorado , Aurora, Colorado ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annaliese J","family":"Calzadilla","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus , Aurora, Colorado ,","place":["USA"]},{"name":"Morgan Adams Foundation Pediatric Brain Tumor Research Program, Children\u2019s Hospital Colorado , Aurora, Colorado ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrique","family":"Grimaldo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus , Aurora, Colorado ,","place":["USA"]},{"name":"Morgan Adams Foundation Pediatric Brain Tumor Research Program, Children\u2019s Hospital Colorado , Aurora, Colorado ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew M","family":"Donson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus , Aurora, Colorado ,","place":["USA"]},{"name":"Morgan Adams Foundation Pediatric Brain Tumor Research Program, Children\u2019s Hospital Colorado , Aurora, Colorado ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lays Martin","family":"Sobral","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus , Aurora, Colorado ,","place":["USA"]},{"name":"Morgan Adams Foundation Pediatric Brain Tumor Research Program, Children\u2019s Hospital Colorado , Aurora, Colorado ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kendra M","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus , Aurora, Colorado ,","place":["USA"]},{"name":"Morgan Adams Foundation Pediatric Brain Tumor Research Program, Children\u2019s Hospital Colorado , Aurora, Colorado ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus , Aurora, Colorado ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir","family":"Amani","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus , Aurora, Colorado ,","place":["USA"]},{"name":"Morgan Adams Foundation Pediatric Brain Tumor Research Program, Children\u2019s Hospital Colorado , Aurora, Colorado ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1512-284X","authenticated-orcid":false,"given":"Sujatha","family":"Venkataraman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus , Aurora, Colorado ,","place":["USA"]},{"name":"Morgan Adams Foundation Pediatric Brain Tumor Research Program, Children\u2019s Hospital Colorado , Aurora, Colorado ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathan A","family":"Dahl","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus , Aurora, Colorado ,","place":["USA"]},{"name":"Morgan Adams Foundation Pediatric Brain Tumor Research Program, Children\u2019s Hospital Colorado , Aurora, Colorado ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean M Mulcahy","family":"Levy","sequence":"additional","affiliation":[{"name":"Clinical Science Graduate Program, Anschutz Medical Campus , Aurora, Colorado ,","place":["USA"]},{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus , Aurora, Colorado ,","place":["USA"]},{"name":"Morgan Adams Foundation Pediatric Brain Tumor Research Program, Children\u2019s Hospital Colorado , Aurora, Colorado ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tzu","family":"Phang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus , Aurora, Colorado ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajeev","family":"Vibhakar","sequence":"additional","affiliation":[{"name":"Clinical Science Graduate Program, Anschutz Medical Campus , Aurora, Colorado ,","place":["USA"]},{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus , Aurora, Colorado ,","place":["USA"]},{"name":"Morgan Adams Foundation Pediatric Brain Tumor Research Program, Children\u2019s Hospital Colorado , Aurora, Colorado ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Todd","family":"Hankinson","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Anschutz Medical Campus , Aurora, Colorado ,","place":["USA"]},{"name":"Morgan Adams Foundation Pediatric Brain Tumor Research Program, Children\u2019s Hospital Colorado , Aurora, Colorado 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