{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T10:23:30Z","timestamp":1782383010008,"version":"3.54.5"},"reference-count":27,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:00:00Z","timestamp":1744070400000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Embryonal tumours with\n                      <jats:italic>PLAGL1<\/jats:italic>\n                      or\n                      <jats:italic>PLAGL2<\/jats:italic>\n                      amplification (ET, PLAGL) show substantial heterogeneity regarding their clinical characteristics and have been treated inconsistently, resulting in diverse outcomes. In this study, we aimed to evaluate the clinical behaviour of ET, PLAGL and elucidate their response pattern across the different applied treatment regimens.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted an in\u2010depth retrospective analysis of clinical and serial imaging data of 18 patients with ET, PLAGL (nine each of\n                      <jats:italic>PLAGL1<\/jats:italic>\n                      and\n                      <jats:italic>PLAGL2<\/jats:italic>\n                      amplified).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Patients with\n                      <jats:italic>PLAGL1<\/jats:italic>\n                      \u2010amplified tumours (ET, PLAGL1) had fewer relapses (3\/9), while\n                      <jats:italic>PLAGL2<\/jats:italic>\n                      \u2010amplified tumours (ET, PLAGL2) were prone to early relapse or progression (8\/9) and to distant, leptomeningeal and intraventricular relapses. Progression\u2010free survival differed significantly between the subtypes (log\u2010rank test,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0055). Postoperative treatment included chemotherapy (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200917, various protocols), alone (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20098) or combined with radiotherapy (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20099). Responses to chemotherapy were observed in both subtypes, and incomplete resection was not associated with inferior survival. All three survivors with ET, PLAGL2 were treated with induction and high\u2010dose chemotherapy with (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091\u2014low\u2010dose CSI and boost) or without (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20092) radiotherapy, whereas five patients with less intensive chemotherapy relapsed. All six survivors with ET, PLAGL1 were treated with conventional chemotherapy regimens, with (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20094\u2014local radiotherapy\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20093; CSI and boost\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091) or without (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20092) radiotherapy. Two patients with ET, PLAGL1 relapsed after 8\u2009years.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Adjuvant therapy should be considered for all ET, PLAGL patients: Patients with ET, PLAGL2 might benefit from intensified chemotherapy regimens. In contrast, patients with ET, PLAGL1 showed superior outcomes without high\u2010dose chemotherapy or craniospinal irradiation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nan.70015","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T08:17:31Z","timestamp":1744100251000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Comparative Clinical and Imaging\u2010Based Evaluation of Therapeutic Modalities in CNS Embryonal Tumours With PLAGL Amplification"],"prefix":"10.1111","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3014-4676","authenticated-orcid":false,"given":"Michaela\u2010Kristina","family":"Keck","sequence":"first","affiliation":[{"name":"Division of Pediatric Glioma Research Hopp Children's Cancer Center Heidelberg (KiTZ)  Heidelberg Germany"},{"name":"National Center for Tumor Diseases (NCT), NCT Heidelberg A Partnership Between DKFZ and Heidelberg University Hospital  Heidelberg Germany"},{"name":"German Cancer Research Center (DKFZ)  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Tietze","sequence":"additional","affiliation":[{"name":"Institute of Neuroradiology Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Bison","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology University Hospital Augsburg  Augsburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shivaram","family":"Avula","sequence":"additional","affiliation":[{"name":"Department of Radiology Alder Hey Children's NHS Foundation Trust  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Engelhardt","sequence":"additional","affiliation":[{"name":"Service de Neurochirurgie B CHU de Bordeaux  Bordeaux France"},{"name":"Universit\u00e9 de Bordeaux, Bordeaux INP, CNRS, IMB, UMR 5251  Talence France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Faure\u2010Conter","sequence":"additional","affiliation":[{"name":"Institut d'Hemato\u2010oncologie Pediatrique  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanguy","family":"Fenouil","sequence":"additional","affiliation":[{"name":"Institut de Pathologie Est, Hospices Civils de Lyon Universit\u00e9 Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre de Recherche en Canc\u00e9rologie de Lyon  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Figarella\u2010Branger","sequence":"additional","affiliation":[{"name":"Aix\u2010Marseille University, APHM, CNRS, INP, Institute De Neurophysiopathologie, CHU Timone Service d'Anatomie Pathologique et de Neuropathologie  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Einar","family":"Goebell","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Interventional Neuroradiology University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Gojo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, Comprehensive Cancer Center and Comprehensive Center for Pediatrics Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Haberler","sequence":"additional","affiliation":[{"name":"Division of Neuropathology and Neurochemistry, Department of Neurology Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juhana","family":"Hakum\u00e4ki","sequence":"additional","affiliation":[{"name":"Department of Clinical Radiology Kuopio University Hospital  Kuopio Finland"},{"name":"Institute of Clinical Medicine University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James\u00a0T.","family":"Hayden","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology Alder Hey Children's NHS Foundation Trust  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura\u00a0S.","family":"Korhonen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine Turku University Hospital and University of Turku  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Koscielniak","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology\/Hematology\/Immunology Olgahospital, Klinikum Stuttgart  Stuttgart Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christof\u00a0M.","family":"Kramm","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology and Oncology University Medical Center G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari\u00ebtte\u00a0E.\u00a0G.","family":"Kranendonk","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten","family":"Lequin","sequence":"additional","affiliation":[{"name":"Division of Imaging and Oncology, Department of Radiology UMC Utrecht  the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise\u00a0E.","family":"Ludlow","sequence":"additional","affiliation":[{"name":"Murdoch Children's Research Institute The Royal Children's Hospital  Parkville Victoria Australia"},{"name":"Children's Cancer Centre The Royal Children's Hospital  Parkville Victoria Australia"},{"name":"Department of Paediatrics The University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Meyronet","sequence":"additional","affiliation":[{"name":"Institut de Pathologie Est, Hospices Civils de Lyon Universit\u00e9 Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre de Recherche en Canc\u00e9rologie de Lyon  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Nyman","sequence":"additional","affiliation":[{"name":"Crown Princess Victoria Children's Hospital Link\u00f6ping University Hospital  Link\u00f6ping Sweden"},{"name":"Department of Biomedical and Clinical Sciences Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"\u00d8ra","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology and Hematology, Sk\u00e5ne University Hospital Lund University  Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Perwein","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hemato\u2010Oncology, Department of Pediatrics and Adolescent Medicine Medical University of Graz  Graz Austria"},{"name":"Styrian Children's Cancer Research\u2014Research Unit for Cancer and Inborn Errors of the Blood and Immunity in Children Medical University of Graz  Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jouni","family":"Pesola","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pediatric Hematology and Oncology Ward, Kuopio University Hospital and Institute of Clinical Medicine University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuomas","family":"Rauramaa","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology, Kuopio University Hospital and Unit of Pathology, Institute of Clinical Medicine University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roel","family":"Reddingius","sequence":"additional","affiliation":[{"name":"Department of Neuro\u2010Oncology Princess M\u00e1xima Center for Pediatric Oncology  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Samuel","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology\u2010Oncology Valley Children's Hospital  Madera California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoinette\u00a0Y.\u00a0N.","family":"Schouten\u2010van\u00a0Meeteren","sequence":"additional","affiliation":[{"name":"Department of Neuro\u2010Oncology Princess M\u00e1xima Center for Pediatric Oncology  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Sexton\u2010Oates","sequence":"additional","affiliation":[{"name":"Rare Cancers Genomics Team, Genomic Epidemiology Branch International Agency for Research on Cancer\/World Health Organization  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Vasiljevic","sequence":"additional","affiliation":[{"name":"Institut de Pathologie Est, Hospices Civils de Lyon Universit\u00e9 Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre de Recherche en Canc\u00e9rologie de Lyon  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thekla","family":"von Kalle","sequence":"additional","affiliation":[{"name":"Department of Radiology Olgahospital, Klinikum Stuttgart  Stuttgart Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika\u00a0K.","family":"Wefers","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"},{"name":"Mildred Scheel Cancer Career Center HaTriCS4 University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter","family":"Wesseling","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"},{"name":"Department of Pathology Amsterdam University Medical Centers, Location VUmc and Brain Tumor Center Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef","family":"Zamecnik","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, Second Faculty of Medicine Charles University and University Hospital Motol  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Zapotocky","sequence":"additional","affiliation":[{"name":"Prague Brain Tumor Research Group, Second Faculty of Medicine Charles University and University Hospital Motol  Prague Czech Republic"},{"name":"Department of Pediatric Haematology and Oncology, Second Faculty of Medicine Charles University and University Hospital Motol  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"von Hoff","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology and Hematology Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt\u2010Universit\u00e4t zu Berlin, and Berlin Institute of Health  Berlin Germany"},{"name":"Department of Paediatric and Adolescent Medicine Aarhus University Hospital  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David\u00a0T.\u00a0W.","family":"Jones","sequence":"additional","affiliation":[{"name":"Division of Pediatric Glioma Research Hopp Children's Cancer Center Heidelberg (KiTZ)  Heidelberg Germany"},{"name":"National Center for Tumor Diseases (NCT), NCT Heidelberg A Partnership Between DKFZ and Heidelberg University Hospital  Heidelberg Germany"},{"name":"German Cancer Research Center (DKFZ)  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,8]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature26000"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3811"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/now101"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noab106"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.CD\u201021\u20101094"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10833"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.1102"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010023\u201002255\u20101"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010021\u201002354\u20108"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010022\u201002516\u20102"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010021\u201002356\u20106"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201020603\u20104"},{"key":"e_1_2_11_14_1","volume-title":"R: A Language and Environment for Statistical Computing","author":"R Core Team","year":"2019"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A7644"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A8496"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(22)00063\u20108"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.01.015"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.281053"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010023\u201002643\u20104"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00381\u2010024\u201006422\u20108"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1148\/93.6.1351"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.02466"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010011\u20100922\u2010z"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2016.02.001"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(15)70114\u20102"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noab136"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2022.104660"}],"container-title":["Neuropathology and Applied Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nan.70015","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/nan.70015","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nan.70015","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T10:45:08Z","timestamp":1779360308000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nan.70015"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4]]},"references-count":27,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1111\/nan.70015"],"URL":"https:\/\/doi.org\/10.1111\/nan.70015","archive":["Portico"],"relation":{},"ISSN":["0305-1846","1365-2990"],"issn-type":[{"value":"0305-1846","type":"print"},{"value":"1365-2990","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4]]},"assertion":[{"value":"2024-11-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70015"}}