{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T01:01:32Z","timestamp":1777942892087,"version":"3.51.4"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100007311","name":"Deutsche Kinderkrebsstiftung","doi-asserted-by":"publisher","award":["DKS 2020.14"],"award-info":[{"award-number":["DKS 2020.14"]}],"id":[{"id":"10.13039\/501100007311","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007311","name":"Deutsche Kinderkrebsstiftung","doi-asserted-by":"publisher","award":["DKS 2024.08"],"award-info":[{"award-number":["DKS 2024.08"]}],"id":[{"id":"10.13039\/501100007311","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2026,6]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n MYCN<\/jats:italic>\n amplification occurs in a subset of retinoblastoma cases, both with and without\n RB1<\/jats:italic>\n inactivation. It has been suggested that retinoblastomas with\n MYCN<\/jats:italic>\n amplification represent a distinct entity with more aggressive clinical behavior.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We examined the incidence of\n MYCN<\/jats:italic>\n gain\/amplification and\n RB1<\/jats:italic>\n inactivation in 192 unilateral retinoblastoma samples from children enucleated between 2011 and 2018 at the German reference center.\n MYCN<\/jats:italic>\n copy number was assessed using quantitative PCR\u00a0and confirmed by single nucleotide polymorphism microarray analysis. Clinical characteristics,\n RB1<\/jats:italic>\n mutation status, and histopathological features were compared between\n MYCN<\/jats:italic>\n \u2010amplified and nonamplified retinoblastomas.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n MYCN<\/jats:italic>\n gain\/amplification was found in 10 of 139 retinoblastomas included in the final analysis (7.2%). All 10 tumors exhibited alterations in at least one\n RB1<\/jats:italic>\n allele (\n RB1<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n or\n RB1<\/jats:italic>\n +\/\u2212<\/jats:sup>\n ). The\n \u00a0RB1<\/jats:italic>\n \u00a0mutation spectrum and overall genomic copy number changes were similar between\n MYCN<\/jats:italic>\n \u2010amplified and\n MYCN<\/jats:italic>\n \u2010nonamplified retinoblastomas. Age at diagnosis did not differ significantly between the two groups (\n p<\/jats:italic>\n \u00a0=\u00a00.21); however, secondary glaucoma, massive choroidal, and scleral invasion occurred more often in\n MYCN<\/jats:italic>\n \u2010amplified retinoblastomas (\n p<\/jats:italic>\n \u00a0=\u00a00.038,\n p<\/jats:italic>\n \u00a0=\u00a00.03, and\n p<\/jats:italic>\n \u00a0=\u00a00.04, respectively). No cases of extraocular retinoblastoma or distant metastasis were observed during a median follow\u2010up of 50 months.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n MYCN<\/jats:italic>\n gain\/amplification was identified in 7.2% of enucleated unilateral retinoblastomas, all of which showed\n \u00a0RB1\u00a0<\/jats:italic>\n inactivation.\n MYCN<\/jats:italic>\n amplification was associated with more advanced disease and more aggressive clinical and histopathological features.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/1545-5017.70297","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T09:55:50Z","timestamp":1775123750000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MYCN<\/i>\n Amplification in\n RB1<\/i>\n \u2010Inactivated Retinoblastoma: Association With High\u2010Risk Features"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8700-082X","authenticated-orcid":false,"given":"Kyriaki","family":"Papaioannou","sequence":"first","affiliation":[{"name":"Department of Pediatrics III University Hospital Essen Essen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Regina","family":"Kubica","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Hospital Essen University of Duisburg\u2010Essen Essen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Fischhuber","sequence":"additional","affiliation":[{"name":"Institute of Biostatistics and Clinical Research University of M\u00fcnster M\u00fcnster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jasmin","family":"Beygo","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Hospital Essen University of Duisburg\u2010Essen Essen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madlen","family":"Reschke","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Oncology and Hematology Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Ritter\u2010Sovinz","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology and Oncology Medical University of Graz Graz Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Biewald","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University Hospital Essen Essen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Ketteler","sequence":"additional","affiliation":[{"name":"Department of Pediatrics III University Hospital Essen Essen Germany"},{"name":"Eye Oncogenetics Research Group University Hospital Essen University of Duisburg\u2010Essen Essen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dietmar","family":"Lohmann","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Hospital Essen University of Duisburg\u2010Essen Essen Germany"},{"name":"Eye Oncogenetics Research Group University Hospital Essen University of Duisburg\u2010Essen Essen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7758-1523","authenticated-orcid":false,"given":"Deniz","family":"Kanber","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Hospital Essen University of Duisburg\u2010Essen Essen Germany"},{"name":"Eye Oncogenetics Research Group University Hospital Essen University of Duisburg\u2010Essen Essen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13071570"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3791\/62939"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.65.1.18"},{"key":"e_1_2_9_5_1","doi-asserted-by":"crossref","unstructured":"V.Raval H.Racher J.Wrenn andA. D.Singh \u201cAqueous Humor as a Surrogate Biomarker for Retinoblastoma Tumor Tissue \u201dJournal of Aapos26 no.3(2022): 137.e1\u2013e5 https:\/\/doi.org\/10.1016\/j.jaapos.2022.03.005.","DOI":"10.1016\/j.jaapos.2022.03.005"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(13)70045\u20107"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.1010"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2018.12.018"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2006.06.018"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.20606"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2020.05.051"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.18.01808"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.120.7.923"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19960315)77:6<1206::AID-CNCR30>3.0.CO;2-3"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/11206721231155671"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.4103\/ijo.IJO_883_16"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41433\u2010020\u20100898\u20109"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2017.4097"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/cjp2.296"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol\u20102018\u2010313005"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xops.2023.100289"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1159\/000533311"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201025792\u20100"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13040754"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201787"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428\u2010025\u201004219\u2010x"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/309458a0"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004280050345"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6600532"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1080\/13816810.2021.1897847"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12092714"}],"container-title":["Pediatric Blood & Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/1545-5017.70297","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/1545-5017.70297","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/1545-5017.70297","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T07:09:56Z","timestamp":1777705796000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/1545-5017.70297"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,2]]},"references-count":30,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1002\/1545-5017.70297"],"URL":"https:\/\/doi.org\/10.1002\/1545-5017.70297","archive":["Portico"],"relation":{},"ISSN":["1545-5009","1545-5017"],"issn-type":[{"value":"1545-5009","type":"print"},{"value":"1545-5017","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,2]]},"assertion":[{"value":"2025-10-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70297"}}