{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T18:21:53Z","timestamp":1790446913050,"version":"4.1.0"},"reference-count":36,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T00:00:00Z","timestamp":1692835200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The identification of cancer predisposition syndromes (CPSs) plays a crucial role in understanding the etiology of pediatric cancers. CPSs are genetic mutations that increase the risk of developing cancer at an earlier age compared to the risk for the general population. This article aims to provide a comprehensive analysis of three unique cases involving pediatric patients with CPS who were diagnosed with multiple simultaneous or metachronous cancers. The first case involves a child with embryonal rhabdomyosarcoma, nephroblastoma, glioma, and subsequent medulloblastoma. Genetic analysis identified two pathogenic variants in the BRCA2 gene. The second case involves a child with alveolar rhabdomyosarcoma, juvenile xanthogranuloma, gliomas, and subsequent JMML\/MDS\/MPS. A pathogenic variant in the NF1 gene was identified. The third case involves a child with pleuropulmonary blastoma and pediatric cystic nephroma\/nephroblastoma, in whom a pathogenic variant in the DICER1 gene was identified. Multiple simultaneous and metachronous cancers in pediatric patients with CPSs are a rare but significant phenomenon. Comprehensive analysis and genetic testing play significant roles in understanding the underlying mechanisms and guiding treatment strategies for these unique cases. Early detection and targeted interventions are important for improving outcomes in these individuals.<\/jats:p>","DOI":"10.3390\/genes14091670","type":"journal-article","created":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T10:09:53Z","timestamp":1692871793000},"page":"1670","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Simultaneous Occurrence of Multiple Neoplasms in Children with Cancer Predisposition Syndromes: Collaborating with Abnormal Genes"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1334-7524","authenticated-orcid":false,"given":"Gabriela","family":"Telman","sequence":"first","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Transplantology, Poznan University of Medical Sciences, Szpitalna 27\/33, 60-572 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8275-3126","authenticated-orcid":false,"given":"Ewa","family":"Strauss","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Polish Academy of Sciences, Strzeszynska 32, 60-479 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4714-6501","authenticated-orcid":false,"given":"Patrycja","family":"Sosnowska-Sienkiewicz","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Traumatology and Urology, Poznan University of Medical Sciences, Szpitalna 27\/33, 60-572 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Halasz","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Transplantology, Poznan University of Medical Sciences, Szpitalna 27\/33, 60-572 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2332-2750","authenticated-orcid":false,"given":"Danuta","family":"Januszkiewicz-Lewandowska","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Transplantology, Poznan University of Medical Sciences, Szpitalna 27\/33, 60-572 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21708","article-title":"Cancer statistics, 2022","volume":"72","author":"Siegel","year":"2022","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/S1470-2045(17)30186-9","article-title":"International incidence of childhood cancer, 2001\u20132010: A population-based registry study","volume":"18","author":"Colombet","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e28335","DOI":"10.1002\/pbc.28335","article-title":"Why do young people get cancer?","volume":"67","author":"Kentsis","year":"2020","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/S1470-2045(18)30909-4","article-title":"Estimating the total incidence of global childhood cancer: A simulation-based analysis","volume":"20","author":"Ward","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1011873","DOI":"10.3389\/fped.2022.1011873","article-title":"Landscape of germline cancer predisposition mutations testing and management in pediatrics: Implications for research and clinical care","volume":"10","author":"Shahani","year":"2022","journal-title":"Front. Pediatr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3008","DOI":"10.1158\/2159-8290.CD-20-1631","article-title":"Genomes for Kids: The Scope of Pathogenic Mutations in Pediatric Cancer Revealed by Comprehensive DNA and RNA Sequencing","volume":"11","author":"Newman","year":"2021","journal-title":"Cancer Discov."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/S2352-4642(20)30275-3","article-title":"Predisposition to cancer in children and adolescents","volume":"5","author":"Kratz","year":"2021","journal-title":"Lancet Child Adolesc. Health"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/s41576-020-00305-9","article-title":"The influence of evolutionary history on human health and disease","volume":"22","author":"Benton","year":"2021","journal-title":"Nat. Rev. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1056\/NEJMoa1508054","article-title":"Germline Mutations in Predisposition Genes in Pediatric Cancer","volume":"373","author":"Zhang","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1097\/MOP.0000000000000857","article-title":"Challenges and solutions to the study of rare childhood tumors","volume":"32","author":"Fair","year":"2020","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1007\/s10897-017-0077-8","article-title":"A Comprehensive Review of Pediatric Tumors and Associated Cancer Predisposition Syndromes","volume":"26","author":"Scollon","year":"2017","journal-title":"J. Genet. Couns."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e133","DOI":"10.1158\/1078-0432.CCR-17-2026","article-title":"The Future of Surveillance in the Context of Cancer Predisposition: Through the Murky Looking Glass","volume":"23","author":"Malkin","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e91","DOI":"10.1158\/1078-0432.CCR-17-0834","article-title":"Genetic Counselor Recommendations for Cancer Predisposition Evaluation and Surveillance in the Pediatric Oncology Patient","volume":"23","author":"Druker","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Krueger, H., McLean, D., and Williams, D. (2008). The Prevention of Second Primary Cancers: A Resource for Clinicians and Health Managers, S. Karger AG.","DOI":"10.1159\/isbn.978-3-8055-8498-2"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zahnreich, S., and Schmidberger, H. (2021). Childhood Cancer: Occurrence, Treatment and Risk of Second Primary Malignancies. Cancers, 13.","DOI":"10.3390\/cancers13112607"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e2254157","DOI":"10.1001\/jamanetworkopen.2022.54157","article-title":"Assessment of Cancer Predisposition Syndromes in a National Cohort of Children with a Neoplasm","volume":"6","author":"Bakhuizen","year":"2023","journal-title":"JAMA Netw. Open"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"137","DOI":"10.4274\/ejbh.galenos.2020.5909","article-title":"The Relationship of Mutation Carriage of BRCA1\/2 and Family History in Triple-Negative Breast Cancer: Experience from a Diagnostic Center in Turkey","volume":"17","author":"Duzkale","year":"2021","journal-title":"Eur. J. Breast Health"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1093\/jnci\/djg072","article-title":"Shared genetic susceptibility to breast cancer, brain tumors, and Fanconi anemia","volume":"95","author":"Offit","year":"2003","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1126\/science.1174334","article-title":"DICER1 mutations in familial pleuropulmonary blastoma","volume":"325","author":"Hill","year":"2009","journal-title":"Science"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3109\/10409238.2015.1117054","article-title":"Dysregulation of microRNA biogenesis machinery in cancer","volume":"51","author":"Hata","year":"2016","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1136\/jmedgenet-2013-101642","article-title":"Fanconi anaemia, BRCA2 mutations and childhood cancer: A developmental perspective from clinical and epidemiological observations with implications for genetic counselling","volume":"51","author":"Meyer","year":"2014","journal-title":"J. Med. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1055\/s-0034-1382021","article-title":"Neurofibromatosis type 1 (NF1) and associated tumors","volume":"226","author":"Rosenbaum","year":"2014","journal-title":"Klin. P\u00e4diatrie"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Robertson, J.C., Jorcyk, C.L., and Oxford, J.T. (2018). DICER1 syndrome: DICER1 mutations in rare cancers. Cancers, 10.","DOI":"10.3390\/cancers10050143"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41379-021-00905-8","article-title":"DICER1 tumor predisposition syndrome: An evolving story initiated with the pleuropulmonary blastoma","volume":"35","author":"Stewart","year":"2022","journal-title":"Mod. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.jpedsurg.2021.08.008","article-title":"Pediatric solid tumors and associated cancer predisposition syndromes: Workup, management, and surveillance. A summary from the APSA Cancer Committee","volume":"57","author":"Grant","year":"2022","journal-title":"J. Pediatr. Surg."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1007\/s13311-022-01277-w","article-title":"Nervous system (NS) Tumors in Cancer Predisposition Syndromes","volume":"19","author":"Patil","year":"2022","journal-title":"Neurotherapeutics"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Woodward, E.R., and Meyer, S. (2021). Fanconi Anaemia, Childhood Cancer and the BRCA Genes. Genes, 12.","DOI":"10.3390\/genes12101520"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"19","DOI":"10.2147\/PHMT.S362679","article-title":"Neurofibromatosis Type 1 (NF1): Addressing the Transition from Pediatric to Adult Care","volume":"14","author":"Radtke","year":"2023","journal-title":"Pediatr. Health Med. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"614541","DOI":"10.3389\/fonc.2020.614541","article-title":"DICER1 Syndrome and Cancer Predisposition: From a Rare Pediatric Tumor to Lifetime Risk","volume":"10","author":"Caroleo","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_30","first-page":"350","article-title":"Why the term \u2018persistent therapy\u2019 is not worse than the term \u2018medical futility\u2019","volume":"48","author":"Ferdynus","year":"2022","journal-title":"J. Med. Ethics"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Rossini, L., Durante, C., Bresolin, S., Opocher, E., Marzollo, A., and Biffi, A. (2022). Diagnostic Strategies and Algorithms for Investigating Cancer Predisposition Syndromes in Children Presenting with Malignancy. Cancers, 14.","DOI":"10.3390\/cancers14153741"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1007\/s00247-021-05023-w","article-title":"Screening of cancer predisposition syndromes","volume":"52","author":"Gottumukkala","year":"2022","journal-title":"Pediatr. Radiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1007\/s00431-021-04347-x","article-title":"The need for tumor surveillance of children and adolescents with cancer predisposition syndromes: A retrospective cohort study in a tertiary-care children\u2019s hospital","volume":"181","author":"Huber","year":"2022","journal-title":"Eur. J. Pediatr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1148\/rg.2021200171","article-title":"Second Malignancies after Radiation Therapy: Update on Pathogenesis and Cross-sectional Imaging Findings","volume":"41","author":"Khanna","year":"2021","journal-title":"Radiographics"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Tanjak, P., Suktitipat, B., Vorasan, N., Juengwiwattanakitti, P., Thiengtrong, B., Songjang, C., Therasakvichya, S., Laiteerapong, S., and Chinswangwatanakul, V. (2021). Risks and cancer associations of metachronous and synchronous multiple primary cancers: A 25-year retrospective study. BMC Cancer, 21.","DOI":"10.1186\/s12885-021-08766-9"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3050","DOI":"10.1200\/JCO.19.00114","article-title":"Subsequent Neoplasms after a Primary Tumor in Individuals with Neurofibromatosis Type 1","volume":"37","author":"Bhatia","year":"2019","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/9\/1670\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:38:03Z","timestamp":1760128683000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/9\/1670"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,24]]},"references-count":36,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["genes14091670"],"URL":"https:\/\/doi.org\/10.3390\/genes14091670","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,24]]}}}