{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T12:45:19Z","timestamp":1786193119597,"version":"build-2736575974"},"reference-count":22,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T00:00:00Z","timestamp":1786147200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T00:00:00Z","timestamp":1786147200000},"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":["American J of Med Genetics Pt A"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    We report a patient with a pathogenic germline variant (PGV) in\n                    <jats:italic>RB1<\/jats:italic>\n                    and somatic mosaicism for a pathogenic\n                    <jats:italic>TP53<\/jats:italic>\n                    variant who developed three distinct types of childhood cancer: retinoblastoma, osteosarcoma, and myelodysplastic syndrome (MDS) before the age of 6\u2009years. The patient presented with bilateral retinoblastoma at age 4\u2009weeks and a PGV in\n                    <jats:italic>RB1<\/jats:italic>\n                    was found. At the very young age of 3\u2009years, she developed an osteosarcoma. A pathogenic variant in\n                    <jats:italic>TP53<\/jats:italic>\n                    was initially found in bone marrow as part of the diagnostic workup for the patient's third cancer, MDS rapidly progressing to acute myeloid leukemia (AML). Due to the unusual clinical phenotype, cultured fibroblasts from a skin biopsy were examined and identified somatic\n                    <jats:italic>TP53<\/jats:italic>\n                    mosaicism, with a VAF of 7%. The early debut of osteosarcoma at age 3\u2009years indicates a stronger predisposition than only heritable retinoblastoma would explain, but the development of subsequent MDS could implicate a vulnerability to chemotherapy due to digenic cancer predisposition. This unusual clinical course underlines the need for a better understanding of genetic predisposition to cancer and the interplay between genetic predisposition and treatment effects in optimizing therapeutic strategies and improving long\u2010term outcomes for these patients.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70256","type":"journal-article","created":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T11:10:05Z","timestamp":1786187405000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Concurrent Germline\n                    <scp>RB1<\/scp>\n                    &amp; Mosaic\n                    <scp>TP53<\/scp>\n                    in a Child With Multiple Childhood Cancers"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3090-6643","authenticated-orcid":false,"given":"Ole Haubjerg","family":"Nielsen","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine Copenhagen University Hospital, Rigshospitalet  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5862-3292","authenticated-orcid":false,"given":"Ulrik Kristoffer","family":"Stoltze","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine Copenhagen University Hospital, Rigshospitalet  Copenhagen Denmark"},{"name":"Department of Clinical Genetics Copenhagen University Hospital, Rigshospitalet  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3424-0590","authenticated-orcid":false,"given":"Pernille Ax\u00e9l","family":"Gregersen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Aarhus University Hospital  Aarhus Denmark"},{"name":"Centre for Rare Diseases, Department of Pediatrics and Adolescent Medicine Aarhus University Hospital  Aarhus Denmark"},{"name":"Department of Clinical Medicine, Health Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine Copenhagen University Hospital, Rigshospitalet  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten Lyng","family":"H\u00f8gild","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Aarhus University Hospital  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mette Klarskov","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Copenhagen University Hospital, Rigshospitalet  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8021-7442","authenticated-orcid":false,"given":"Lise Barlebo","family":"Ahlborn","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine Copenhagen University Hospital, Rigshospitalet  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa Lyngsie","family":"Hjalgrim","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine Copenhagen University Hospital, Rigshospitalet  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin A. W.","family":"Wadt","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Copenhagen University Hospital, Rigshospitalet  Copenhagen Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,8]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.59.5728"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1009231"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.34163"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/PO.20.00087"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/ced\/llaf064"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-020-0638-4"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr310"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1842-9"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201024\u20103271"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.01096"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.68.4.820"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.14106"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djv101"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.983668"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics11010028"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2017-104976"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.31362"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom12101350"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2019.10.002"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22883"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-023-01167-6"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.257246.119"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.70256","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.70256","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.70256","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T12:08:16Z","timestamp":1786190896000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.70256"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,8]]},"references-count":22,"alternative-id":["10.1002\/ajmg.a.70256"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.70256","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,8]]},"assertion":[{"value":"2026-01-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"ajmg.a.70256"}}