{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:11:04Z","timestamp":1792782664231,"version":"4.5.0"},"reference-count":57,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"The Morgan Adams Foundation","id":[{"id":"https:\/\/ror.org\/00ghy1a10","id-type":"ROR","asserted-by":"crossref"}]},{"name":"The Team Ax Foundation"},{"name":"The Olivia Caldwell Foundation"},{"name":"The Tanner Seebaum Foundation","id":[{"id":"https:\/\/ror.org\/04ngsnt90","id-type":"ROR","asserted-by":"crossref"}]},{"name":"The Team Jack Foundation"},{"name":"University of Colorado Cancer Center","award":["P30CA046934"],"award-info":[{"award-number":["P30CA046934"]}],"id":[{"id":"https:\/\/ror.org\/04cqn7d42","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Fighting Ependymoma"},{"name":"The James Tudor Foundation","id":[{"id":"https:\/\/ror.org\/02h4ww944","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Acta Neuropathol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Posterior Fossa A (PFA) is the most frequent and clinically aggressive ependymoma (EPN) subgroup, with relapse typically representing a terminal event despite intensive multimodal therapy. Ultra-high-risk PFA EPNs are characterised by chromosome 6q loss (6q-) with or without chromosome 1q gain (1q\u2009+). While the molecular mechanisms driving 1q+ have been elucidated, 6q- PFA pathobiology remains poorly understood. Here, we show that loss of 6q in PFA EPN results in deletion of\n                    <jats:italic>LATS1<\/jats:italic>\n                    (Large Tumour Suppressor Kinase 1), thereby dysregulating the Hippo signalling pathway and enhancing YAP\/TEAD activity. Integrated analyses of primary and recurrent PFA EPNs, incorporating clinical, multiomic, and functional assays, were performed to define the biology and therapeutic susceptibility of 6q- PFA EPNs. Cumulative 6q loss was associated with nearly half of PFA EPN-related deaths. Copy number profiling identified the\n                    <jats:italic>LATS1<\/jats:italic>\n                    locus as recurrently deleted across all 6q- cases, including 10\/60 with partial 6q deletions. Restoration of\n                    <jats:italic>LATS1<\/jats:italic>\n                    expression in 6q- PFA cell lines re-established protein levels and suppressed proliferation. Tumour analyses showed marked Hippo pathway disruption with elevated YAP expression and\n                    <jats:italic>TEAD2-<\/jats:italic>\n                    related transcriptional activity. TEAD2 palmitoylation inhibitor VT107, and Proteolysis Targeted Chimera (PROTAC) degrader H122, exhibited PFA 6q- selective activity in vitro.\n                    <jats:italic>TEAD2<\/jats:italic>\n                    upregulation was further observed in a previously described undifferentiated, progenitor-like population of PFA EPN cells. In conclusion, 6q loss defines an aggressive biological subset of PFA associated with dismal outcomes. Identification of\n                    <jats:italic>LATS1<\/jats:italic>\n                    as a recurrently lost tumour suppressor implicates Hippo pathway dysregulation as a central driver of malignancy, and we identify YAP\/TEAD signalling as a potential therapeutic target.\n                  <\/jats:p>","DOI":"10.1007\/s00401-026-03098-z","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:54:11Z","timestamp":1791921251000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chromosome 6q mediated loss of LATS1 tumour suppression as a targetable mechanism of ultra-high-risk posterior fossa A ependymoma"],"prefix":"10.1007","volume":"152","author":[{"given":"Andrew M.","family":"Donson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea M.","family":"Griesinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca J.","family":"Chapman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard G.","family":"Grundy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John-Paul","family":"Kilday","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay","family":"Ramaswamy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean M. Mulcahy","family":"Levy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Kaufman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Amani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia K.","family":"Sundheimer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian W.","family":"Pajtler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas K.","family":"Foreman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy A.","family":"Ritzmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,13]]},"reference":[{"key":"3098_CR1","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1093\/jnen\/nlx040","volume":"76","author":"V Amani","year":"2017","unstructured":"Amani V, Donson AM, Lummus SC, Prince EW, Griesinger AM, Witt DA et al (2017) Characterization of 2 novel ependymoma cell lines with chromosome 1q gain derived from posterior fossa tumors of childhood. J Neuropathol Exp Neurol 76:595\u2013604. https:\/\/doi.org\/10.1093\/jnen\/nlx040","journal-title":"J Neuropathol Exp Neurol"},{"key":"3098_CR2","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1186\/s40478-016-0349-9","volume":"4","author":"A Araki","year":"2016","unstructured":"Araki A, Chocholous M, Gojo J, Dorfer C, Czech T, Heinzl H et al (2016) Chromosome 1q gain and tenascin-C expression are candidate markers to define different risk groups in pediatric posterior fossa ependymoma. Acta Neuropathol Commun 4:88. https:\/\/doi.org\/10.1186\/s40478-016-0349-9","journal-title":"Acta Neuropathol Commun"},{"key":"3098_CR3","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/j.cell.2018.02.060","volume":"173","author":"MH Bailey","year":"2018","unstructured":"Bailey MH, Tokheim C, Porta-Pardo E, Sengupta S, Bertrand D, Weerasinghe A et al (2018) Comprehensive characterization of cancer driver genes and mutations. Cell 173:371-385.e18. https:\/\/doi.org\/10.1016\/j.cell.2018.02.060","journal-title":"Cell"},{"key":"3098_CR4","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1038\/nature08460","volume":"462","author":"DA Barbie","year":"2009","unstructured":"Barbie DA, Tamayo P, Boehm JS, Kim SY, Moody SE, Dunn IF et al (2009) Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1. Nature 462:108\u2013112. https:\/\/doi.org\/10.1038\/nature08460","journal-title":"Nature"},{"key":"3098_CR5","doi-asserted-by":"publisher","first-page":"1360","DOI":"10.1093\/neuonc\/noab034","volume":"23","author":"LV Baroni","year":"2021","unstructured":"Baroni LV, Sundaresan L, Heled A, Coltin H, Pajtler KW, Lin T et al (2021) Ultra high-risk PFA ependymoma is characterized by loss of chromosome 6q. Neuro Oncol 23:1360\u20131370. https:\/\/doi.org\/10.1093\/neuonc\/noab034","journal-title":"Neuro Oncol"},{"key":"3098_CR6","doi-asserted-by":"publisher","first-page":"3320","DOI":"10.1101\/gad.1726608","volume":"22","author":"X Cao","year":"2008","unstructured":"Cao X, Pfaff SL, Gage FH (2008) YAP regulates neural progenitor cell number via the TEA domain transcription factor. Genes Dev 22:3320\u20133334. https:\/\/doi.org\/10.1101\/gad.1726608","journal-title":"Genes Dev"},{"key":"3098_CR7","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1093\/neuonc\/noad207","volume":"26","author":"J DeSisto","year":"2024","unstructured":"DeSisto J, Donson AM, Griesinger AM, Fu R, Riemondy K, Mulcahy Levy J et al (2024) Tumor and immune cell types interact to produce heterogeneous phenotypes of pediatric high-grade glioma. Neuro Oncol 26:538\u2013552. https:\/\/doi.org\/10.1093\/neuonc\/noad207","journal-title":"Neuro Oncol"},{"key":"3098_CR8","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S et al (2013) STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29:15\u201321. https:\/\/doi.org\/10.1093\/bioinformatics\/bts635","journal-title":"Bioinformatics"},{"key":"3098_CR9","doi-asserted-by":"publisher","first-page":"1984","DOI":"10.1158\/1535-7163.MCT-17-1185","volume":"17","author":"AM Donson","year":"2018","unstructured":"Donson AM, Amani V, Warner EA, Griesinger AM, Witt DA, Levy JMM et al (2018) Identification of FDA-approved oncology drugs with selective potency in high-risk childhood ependymoma. Mol Cancer Ther 17:1984\u20131994. https:\/\/doi.org\/10.1158\/1535-7163.MCT-17-1185","journal-title":"Mol Cancer Ther"},{"key":"3098_CR10","doi-asserted-by":"publisher","first-page":"1854","DOI":"10.1093\/neuonc\/noad096","volume":"25","author":"AM Donson","year":"2023","unstructured":"Donson AM, Bertrand KC, Riemondy KA, Gao D, Zhuang Y, Sanford B et al (2023) Significant increase of high-risk chromosome 1q gain and 6q loss at recurrence in posterior fossa group A ependymoma: a multicenter study. Neuro Oncol 25:1854\u20131867. https:\/\/doi.org\/10.1093\/neuonc\/noad096","journal-title":"Neuro Oncol"},{"key":"3098_CR11","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16167-y","volume":"11","author":"N Eder","year":"2020","unstructured":"Eder N, Roncaroli F, Domart M-C, Horswell S, Andreiuolo F, Flynn HR et al (2020) YAP1\/TAZ drives ependymoma-like tumour formation in mice. Nat Commun 11:2380. https:\/\/doi.org\/10.1038\/s41467-020-16167-y","journal-title":"Nat Commun"},{"key":"3098_CR12","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9010128","volume":"9","author":"RM Engel","year":"2020","unstructured":"Engel RM, Chan WH, Nickless D, Hlavca S, Richards E, Kerr G et al (2020) Patient-derived colorectal cancer organoids upregulate revival stem cell marker genes following chemotherapeutic treatment. J Clin Med 9:128. https:\/\/doi.org\/10.3390\/jcm9010128","journal-title":"J Clin Med"},{"key":"3098_CR13","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noac219","author":"R Fu","year":"2022","unstructured":"Fu R, Norris GA, Willard N, Griesinger AM, Riemondy KA, Amani V et al (2022) Spatial transcriptomic analysis delineates epithelial and mesenchymal subpopulations and transition stages in childhood ependymoma. Neuro Oncol. https:\/\/doi.org\/10.1093\/neuonc\/noac219","journal-title":"Neuro Oncol"},{"key":"3098_CR14","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108023","author":"AE Gillen","year":"2020","unstructured":"Gillen AE, Riemondy KA, Amani V, Griesinger AM, Gilani A, Venkataraman S et al (2020) Single-Cell RNA sequencing of childhood ependymoma reveals neoplastic cell subpopulations that impact molecular classification and etiology. Cell Rep. https:\/\/doi.org\/10.1016\/j.celrep.2020.108023","journal-title":"Cell Rep"},{"key":"3098_CR15","doi-asserted-by":"publisher","first-page":"1544","DOI":"10.1158\/1078-0432.CCR-23-3156","volume":"30","author":"AM Griesinger","year":"2024","unstructured":"Griesinger AM, Calzadilla AJ, Grimaldo E, Donson AM, Amani V, Pierce AM et al (2024) Development of chromosome 1q+ specific treatment for highest risk pediatric posterior fossa ependymoma. Clin Cancer Res 30:1544\u20131554. https:\/\/doi.org\/10.1158\/1078-0432.CCR-23-3156","journal-title":"Clin Cancer Res"},{"key":"3098_CR16","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.107585","volume":"26","author":"AM Griesinger","year":"2023","unstructured":"Griesinger AM, Riemondy K, Eswaran N, Donson AM, Willard N, Prince EW et al (2023) Multi-omic approach identifies hypoxic tumor-associated myeloid cells that drive immunobiology of high-risk pediatric ependymoma. iScience 26:107585. https:\/\/doi.org\/10.1016\/j.isci.2023.107585","journal-title":"iScience"},{"key":"3098_CR17","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1186\/s12967-019-1869-4","volume":"17","author":"Y Han","year":"2019","unstructured":"Han Y (2019) Analysis of the role of the Hippo pathway in cancer. J Transl Med 17:116. https:\/\/doi.org\/10.1186\/s12967-019-1869-4","journal-title":"J Transl Med"},{"key":"3098_CR18","doi-asserted-by":"publisher","first-page":"5496","DOI":"10.1074\/jbc.M709037200","volume":"283","author":"Y Hao","year":"2008","unstructured":"Hao Y, Chun A, Cheung K, Rashidi B, Yang X (2008) Tumor suppressor LATS1 is a negative regulator of oncogene YAP. J Biol Chem 283:5496\u20135509. https:\/\/doi.org\/10.1074\/jbc.M709037200","journal-title":"J Biol Chem"},{"key":"3098_CR19","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2020.172981","volume":"873","author":"AP Harrold","year":"2020","unstructured":"Harrold AP, Cleary MM, Bharathy N, Lathara M, Berlow NE, Foreman NK et al (2020) In vitro benchmarking of NF-\u03baB inhibitors. Eur J Pharmacol 873:172981. https:\/\/doi.org\/10.1016\/j.ejphar.2020.172981","journal-title":"Eur J Pharmacol"},{"key":"3098_CR20","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-025-01234-0","author":"KF Harvey","year":"2025","unstructured":"Harvey KF, Tang TT (2025) Targeting the Hippo pathway in cancer. Nat Rev Drug Discov. https:\/\/doi.org\/10.1038\/s41573-025-01234-0","journal-title":"Nat Rev Drug Discov"},{"key":"3098_CR21","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noaf218","author":"K von Hoff","year":"2025","unstructured":"von Hoff K, Obrecht-Sturm D, Ghasemi DR, Wenning J, Mynarek M, Gerber NU et al (2025) Developing an advanced risk stratification model for pediatric intracranial ependymoma based on the prospective trial E-HIT2000 and subsequent registries. Neuro Oncol. https:\/\/doi.org\/10.1093\/neuonc\/noaf218","journal-title":"Neuro Oncol"},{"key":"3098_CR22","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1053\/j.gastro.2022.05.007","volume":"163","author":"S Hu","year":"2022","unstructured":"Hu S, Molina L, Tao J, Liu S, Hassan M, Singh S et al (2022) NOTCH-YAP1\/TEAD-DNMT1 axis drives hepatocyte reprogramming into intrahepatic cholangiocarcinoma. Gastroenterology 163:449\u2013465. https:\/\/doi.org\/10.1053\/j.gastro.2022.05.007","journal-title":"Gastroenterology"},{"key":"3098_CR23","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1007\/s00401-001-0479-3","volume":"103","author":"B Huang","year":"2002","unstructured":"Huang B, Starostik P, K\u00fchl J, Tonn J, Roggendorf W (2002) Loss of heterozygosity on chromosome 22 in human ependymomas. Acta Neuropathol 103:415\u2013420. https:\/\/doi.org\/10.1007\/s00401-001-0479-3","journal-title":"Acta Neuropathol"},{"key":"3098_CR24","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-026-10270-8","author":"AS Kardian","year":"2026","unstructured":"Kardian AS, Sun H, Ippagunta S, Laboe N, Varadharajan S, Yu K et al (2026) Dominant clones leverage developmental epigenomic states to drive ependymoma. Nature. https:\/\/doi.org\/10.1038\/s41586-026-10270-8","journal-title":"Nature"},{"key":"3098_CR25","doi-asserted-by":"publisher","first-page":"2001","DOI":"10.1158\/1078-0432.CCR-11-2489","volume":"18","author":"JP Kilday","year":"2012","unstructured":"Kilday JP, Mitra B, Domerg C, Ward J, Andreiuolo F, Osteso-Ibanez T et al (2012) Copy number gain of 1q25 predicts poor progression-free survival for pediatric intracranial ependymomas and enables patient risk stratification: a prospective european clinical trial cohort analysis on behalf of the Children\u2019s Cancer Leukaemia Group (CCLG. Clin Cancer Res 18:2001\u20132011. https:\/\/doi.org\/10.1158\/1078-0432.CCR-11-2489","journal-title":"Clin Cancer Res"},{"key":"3098_CR26","doi-asserted-by":"publisher","first-page":"16135","DOI":"10.1021\/acs.jmedchem.6c02076","volume":"69","author":"A Kumar","year":"2026","unstructured":"Kumar A, Ali S, Shen Q, Zhou J (2026) FDA approval of the first-ever PROTAC: Vepdegestrant (ARV-471) marks a new era in targeted protein degradation. J Med Chem 69:16135\u201316142. https:\/\/doi.org\/10.1021\/acs.jmedchem.6c02076","journal-title":"J Med Chem"},{"key":"3098_CR27","doi-asserted-by":"publisher","first-page":"5616","DOI":"10.1021\/acs.jmedchem.4c02884","volume":"68","author":"Y Lu","year":"2025","unstructured":"Lu Y, Yan Z, Sun J, Wang C, Xu L, Lyu X et al (2025) Selective degradation of TEADs by a PROTAC molecule exhibited robust anticancer efficacy in vitro and in vivo. J Med Chem 68:5616\u20135640. https:\/\/doi.org\/10.1021\/acs.jmedchem.4c02884","journal-title":"J Med Chem"},{"key":"3098_CR28","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1146\/annurev-biochem-013118-111829","volume":"88","author":"S Ma","year":"2019","unstructured":"Ma S, Meng Z, Chen R, Guan K-L (2019) The Hippo pathway: biology and pathophysiology. Annu Rev Biochem 88:577\u2013604. https:\/\/doi.org\/10.1146\/annurev-biochem-013118-111829","journal-title":"Annu Rev Biochem"},{"key":"3098_CR29","doi-asserted-by":"publisher","first-page":"2070","DOI":"10.1158\/1078-0432.CCR-05-2363","volume":"12","author":"F Mendrzyk","year":"2006","unstructured":"Mendrzyk F, Korshunov A, Benner A, Toedt G, Pfister S, Radlwimmer B et al (2006) Identification of gains on 1q and epidermal growth factor receptor overexpression as independent prognostic markers in intracranial ependymoma. Clin Cancer Res 12:2070\u20132079. https:\/\/doi.org\/10.1158\/1078-0432.CCR-05-2363","journal-title":"Clin Cancer Res"},{"key":"3098_CR30","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1007\/s00401-011-0866-3","volume":"122","author":"T Milde","year":"2011","unstructured":"Milde T, Kleber S, Korshunov A, Witt H, Hielscher T, Koch P et al (2011) A novel human high-risk ependymoma stem cell model reveals the differentiation-inducing potential of the histone deacetylase inhibitor Vorinostat. Acta Neuropathol 122:637\u2013650. https:\/\/doi.org\/10.1007\/s00401-011-0866-3","journal-title":"Acta Neuropathol"},{"key":"3098_CR31","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11884-5","volume":"10","author":"KW Pajtler","year":"2019","unstructured":"Pajtler KW, Wei Y, Okonechnikov K, Silva PBG, Vouri M, Zhang L et al (2019) YAP1 subgroup supratentorial ependymoma requires TEAD and nuclear factor I-mediated transcriptional programmes for tumorigenesis. Nat Commun 10:3914. https:\/\/doi.org\/10.1038\/s41467-019-11884-5","journal-title":"Nat Commun"},{"key":"3098_CR32","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1877-0","author":"KW Pajtler","year":"2018","unstructured":"Pajtler KW, Wen J, Sill M, Lin T, Orisme W, Tang B et al (2018) Molecular heterogeneity and CXorf67 alterations in posterior fossa group A (PFA) ependymomas. Acta Neuropathol. https:\/\/doi.org\/10.1007\/s00401-018-1877-0","journal-title":"Acta Neuropathol"},{"key":"3098_CR33","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1016\/j.ccell.2015.04.002","volume":"27","author":"KW Pajtler","year":"2015","unstructured":"Pajtler KW, Witt H, Sill M, Jones DTW, Hovestadt V, Kratochwil F et al (2015) Molecular classification of ependymal tumors across all CNS compartments, histopathological grades, and age groups. Cancer Cell 27:728\u2013743. https:\/\/doi.org\/10.1016\/j.ccell.2015.04.002","journal-title":"Cancer Cell"},{"key":"3098_CR34","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1016\/j.devcel.2010.09.011","volume":"19","author":"D Pan","year":"2010","unstructured":"Pan D (2010) The Hippo signaling pathway in development and cancer. Dev Cell 19:491\u2013505. https:\/\/doi.org\/10.1016\/j.devcel.2010.09.011","journal-title":"Dev Cell"},{"key":"3098_CR35","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7910","volume":"6","author":"R Pathania","year":"2015","unstructured":"Pathania R, Ramachandran S, Elangovan S, Padia R, Yang P, Cinghu S et al (2015) DNMT1 is essential for mammary and cancer stem cell maintenance and tumorigenesis. Nat Commun 6:6910. https:\/\/doi.org\/10.1038\/ncomms7910","journal-title":"Nat Commun"},{"key":"3098_CR36","doi-asserted-by":"publisher","DOI":"10.1016\/j.mbplus.2021.100074","volume":"12","author":"MC Primi","year":"2021","unstructured":"Primi MC, Rangarajan ES, Patil DN, Izard T (2021) Conformational flexibility determines the Nf2\/merlin tumor suppressor functions. Matrix Biol Plus 12:100074. https:\/\/doi.org\/10.1016\/j.mbplus.2021.100074","journal-title":"Matrix Biol Plus"},{"key":"3098_CR37","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1093\/neuonc\/noab135","volume":"24","author":"KA Riemondy","year":"2022","unstructured":"Riemondy KA, Venkataraman S, Willard N, Nellan A, Sanford B, Griesinger AM et al (2022) Neoplastic and immune single-cell transcriptomics define subgroup-specific intra-tumoral heterogeneity of childhood medulloblastoma. Neuro Oncol 24:273\u2013286. https:\/\/doi.org\/10.1093\/neuonc\/noab135","journal-title":"Neuro Oncol"},{"key":"3098_CR38","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noac012","author":"TA Ritzmann","year":"2022","unstructured":"Ritzmann TA, Chapman RJ, Kilday J-P, Thorp N, Modena P, Dineen RA et al (2022) SIOP Ependymoma I: final results, long-term follow-up, and molecular analysis of the trial cohort\u2014A BIOMECA Consortium Study. Neuro Oncol. https:\/\/doi.org\/10.1093\/neuonc\/noac012","journal-title":"Neuro Oncol"},{"key":"3098_CR39","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1093\/neuonc\/noab066","volume":"23","author":"TA Ritzmann","year":"2021","unstructured":"Ritzmann TA, Kilday JP, Grundy RG (2021) Pediatric ependymomas: destined to recur? Neuro Oncol 23:874\u2013876","journal-title":"Neuro Oncol"},{"key":"3098_CR40","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.28426","author":"TA Ritzmann","year":"2020","unstructured":"Ritzmann TA, Rogers HA, Paine SML, Storer LCD, Jacques TS, Chapman RJ et al (2020) A retrospective analysis of recurrent pediatric ependymoma reveals extremely poor survival and ineffectiveness of current treatments across central nervous system locations and molecular subgroups. Pediatr Blood Cancer. https:\/\/doi.org\/10.1002\/pbc.28426","journal-title":"Pediatr Blood Cancer"},{"key":"3098_CR41","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1038\/ng1068","volume":"33","author":"M-F Robert","year":"2003","unstructured":"Robert M-F, Morin S, Beaulieu N, Gauthier F, Chute IC, Barsalou A et al (2003) DNMT1 is required to maintain CpG methylation and aberrant gene silencing in human cancer cells. Nat Genet 33:61\u201365. https:\/\/doi.org\/10.1038\/ng1068","journal-title":"Nat Genet"},{"key":"3098_CR42","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcped.2025.100227","volume":"5","author":"A Rubio-San-Sim\u00f3n","year":"2025","unstructured":"Rubio-San-Sim\u00f3n A, Ritzmann TA, Obrecht-Sturm D, Benesch M, Timmermann B, Leblond P et al (2025) European standard clinical practice recommendations for newly diagnosed ependymoma of childhood and adolescence. EJC Paediatr Oncol 5:100227. https:\/\/doi.org\/10.1016\/j.ejcped.2025.100227","journal-title":"EJC Paediatr Oncol"},{"key":"3098_CR43","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1038\/s41568-022-00497-8","volume":"22","author":"A Sharma","year":"2022","unstructured":"Sharma A, Bl\u00e9riot C, Currenti J, Ginhoux F (2022) Oncofetal reprogramming in tumour development and progression. Nat Rev Cancer 22:593\u2013602. https:\/\/doi.org\/10.1038\/s41568-022-00497-8","journal-title":"Nat Rev Cancer"},{"key":"3098_CR44","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1007\/s00401-021-02356-6","volume":"142","author":"P Sievers","year":"2021","unstructured":"Sievers P, Henneken SC, Blume C, Sill M, Schrimpf D, Stichel D et al (2021) Recurrent fusions in PLAGL1 define a distinct subset of pediatric-type supratentorial neuroepithelial tumors. Acta Neuropathol 142:827\u2013839. https:\/\/doi.org\/10.1007\/s00401-021-02356-6","journal-title":"Acta Neuropathol"},{"key":"3098_CR45","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","volume":"102","author":"A Subramanian","year":"2005","unstructured":"Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA et al (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A 102:15545\u201315550. https:\/\/doi.org\/10.1073\/pnas.0506580102","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3098_CR46","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-019-0101-6","volume":"4","author":"X Sun","year":"2019","unstructured":"Sun X, Gao H, Yang Y, He M, Wu Y, Song Y et al (2019) PROTACs: great opportunities for academia and industry. Signal Transduct Target Ther 4:64. https:\/\/doi.org\/10.1038\/s41392-019-0101-6","journal-title":"Signal Transduct Target Ther"},{"key":"3098_CR47","doi-asserted-by":"publisher","DOI":"10.1172\/JCI193332","author":"AC Tallon-Cobos","year":"2026","unstructured":"Tallon-Cobos AC, Vazaios K, Waranecki P, van Hoesel M, Cornel A, Schwalm B et al (2026) CAR T cells targeting the glycoprotein GD2 show potent antitumor efficacy in high-risk ependymoma models. J Clin Invest. https:\/\/doi.org\/10.1172\/JCI193332","journal-title":"J Clin Invest"},{"key":"3098_CR48","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1158\/1535-7163.MCT-20-0717","volume":"20","author":"TT Tang","year":"2021","unstructured":"Tang TT, Konradi AW, Feng Y, Peng X, Ma M, Li J et al (2021) Small molecule inhibitors of TEAD auto-palmitoylation selectively inhibit proliferation and tumor growth of NF2-deficient mesothelioma. Mol Cancer Ther 20:986\u2013998. https:\/\/doi.org\/10.1158\/1535-7163.MCT-20-0717","journal-title":"Mol Cancer Ther"},{"key":"3098_CR49","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.trecan.2023.11.003","volume":"10","author":"CJ Tape","year":"2024","unstructured":"Tape CJ (2024) Plastic persisters: revival stem cells in colorectal cancer. Trends Cancer 10:185\u2013195. https:\/\/doi.org\/10.1016\/j.trecan.2023.11.003","journal-title":"Trends Cancer"},{"key":"3098_CR50","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1038\/nprot.2012.016","volume":"7","author":"C Trapnell","year":"2012","unstructured":"Trapnell C, Roberts A, Goff L, Pertea G, Kim D, Kelley DR et al (2012) Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat Protoc 7:562\u2013578. https:\/\/doi.org\/10.1038\/nprot.2012.016","journal-title":"Nat Protoc"},{"key":"3098_CR51","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1007\/s00401-012-0941-4","volume":"123","author":"K Wani","year":"2012","unstructured":"Wani K, Armstrong TS, Vera-Bolanos E, Raghunathan A, Ellison D, Gilbertson R et al (2012) A prognostic gene expression signature in infratentorial ependymoma. Acta Neuropathol 123:727\u2013738. https:\/\/doi.org\/10.1007\/s00401-012-0941-4","journal-title":"Acta Neuropathol"},{"key":"3098_CR52","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.26960","volume":"65","author":"DA Witt","year":"2018","unstructured":"Witt DA, Donson AM, Amani V, Moreira DC, Sanford B, Hoffman LM et al (2018) Specific expression of PD-L1 in RELA-fusion supratentorial ependymoma: implications for PD-1-targeted therapy. Pediatr Blood Cancer 65:e26960. https:\/\/doi.org\/10.1002\/pbc.26960","journal-title":"Pediatr Blood Cancer"},{"key":"3098_CR53","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.ccr.2011.07.007","volume":"20","author":"H Witt","year":"2011","unstructured":"Witt H, Mack SC, Ryzhova M, Bender S, Sill M, Isserlin R et al (2011) Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma. Cancer Cell 20:143\u2013157. https:\/\/doi.org\/10.1016\/j.ccr.2011.07.007","journal-title":"Cancer Cell"},{"key":"3098_CR54","doi-asserted-by":"publisher","first-page":"4281","DOI":"10.1038\/s41591-025-04029-3","volume":"31","author":"TA Yap","year":"2025","unstructured":"Yap TA, Kwiatkowski DJ, Dagogo-Jack I, Offin M, Zauderer MG, Kratzke R et al (2025) YAP\/TEAD inhibitor VT3989 in solid tumors: a phase 1\/2 trial. Nat Med 31:4281\u20134290. https:\/\/doi.org\/10.1038\/s41591-025-04029-3","journal-title":"Nat Med"},{"key":"3098_CR55","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1534\/genetics.113.156372","volume":"195","author":"T Yu","year":"2013","unstructured":"Yu T, Bachman J, Lai Z-C (2013) Evidence for a tumor suppressor role for the large tumor suppressor genes LATS1 and LATS2 in human cancer. Genetics 195:1193\u20131196. https:\/\/doi.org\/10.1534\/genetics.113.156372","journal-title":"Genetics"},{"key":"3098_CR56","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1007\/s00381-009-1067-4","volume":"26","author":"S Zacharoulis","year":"2010","unstructured":"Zacharoulis S, Ashley S, Moreno L, Gentet JC, Massimino M, Frappaz D (2010) Treatment and outcome of children with relapsed ependymoma: a multi-institutional retrospective analysis. Childs Nerv Syst 26:905\u2013911. https:\/\/doi.org\/10.1007\/s00381-009-1067-4","journal-title":"Childs Nerv Syst"},{"key":"3098_CR57","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.70023","author":"S Zahedi","year":"2025","unstructured":"Zahedi S, Riemondy K, Liu T, Griesinger AM, Donson AM, Apfelbaum AA et al (2025) Multi-pronged analysis of pediatric low-grade glioma and ganglioglioma reveals a unique tumor microenvironment associated with BRAF alterations. Brain Pathology. https:\/\/doi.org\/10.1111\/bpa.70023","journal-title":"Brain Pathology"}],"container-title":["Acta Neuropathologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-026-03098-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00401-026-03098-z","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-026-03098-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:06:46Z","timestamp":1791950806000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00401-026-03098-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,13]]},"references-count":57,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["3098"],"URL":"https:\/\/doi.org\/10.1007\/s00401-026-03098-z","relation":{},"ISSN":["1432-0533"],"issn-type":[{"value":"1432-0533","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,13]]},"assertion":[{"value":"19 May 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 September 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 September 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 October 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors have no conflicts of interest to declare.","order":1,"name":"Ethics","label":"Conflicts of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Copy number profiles were from previously published datasets. Newly generated data\u2014including bulk RNA sequencing, immunohistochemistry, and Xenium assays\u2014were collected from specimens obtained during routine surgical procedures or autopsy, in accordance with institutional guidelines and with informed patient consent (COMIRB 95\u2013500).","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"52"}}