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- Title
Assessment of Cancer Predisposition Syndromes in a National Cohort of Children With a Neoplasm.
- Authors
Bakhuizen, Jette J.; Hopman, Saskia M. J.; Bosscha, Machteld I.; Dommering, Charlotte J.; van den Heuvel-Eibrink, Marry M.; Hol, Janna A.; Kester, Lennart A.; Koudijs, Marco J.; Langenberg, Karin P. S.; Loeffen, Jan L. C.; van der Lugt, Jasper; Moll, Annette C.; van Noesel, Max M.; Smetsers, Stephanie E.; de Vos-Kerkhof, Evelien; Merks, Johannes H. M.; Kuiper, Roland P.; Jongmans, Marjolijn C. J.
- Abstract
Key Points: Question: What is the diagnostic yield of phenotype-driven genetic testing in children with cancer? Findings: In this unselected cohort study of 824 Dutch children with a neoplasm, a cancer predisposition syndrome was found in 71 patients (8.6%), of which most (96%) were identified by a phenotype-driven approach. Meaning: The diagnostic approach for identifying genetic predisposition in children with cancer is increasingly shifting toward a genotype-first approach; the findings from this phenotype-driven cohort can potentially be used as reference for future genotype-driven studies. Importance: To improve diagnostics of cancer predisposition syndromes (CPSs) in children with cancer, it is essential to evaluate the effect of CPS gene sequencing among all children with cancer and compare it with genetic testing based on clinical selection. However, a reliable comparison is difficult because recent reports on a phenotype-first approach in large, unselected childhood cancer cohorts are lacking. Objective: To describe a national children's cancer center's experience in diagnosing CPSs before introducing routine next-generation sequencing. Design, Setting, and Participants: This retrospective cohort study was conducted at the National Retinoblastoma Treatment Center (Amsterdam, the Netherlands) and the Princess Máxima Center for Pediatric Oncology (Utrecht, Netherlands) and included Dutch pediatric patients with a new diagnosis of neoplasm between June 1, 2018, and December 31, 2019. Follow-up was at least 18 months after neoplasm diagnosis. Data analysis was conducted from July 2021 to February 2022. Exposures: As part of routine diagnostics, pediatric oncologists and ophthalmologists checked for characteristics of CPSs and selected children for referral to clinical geneticists and genetic testing. Main Outcomes and Measures: Detected cancer predisposition syndromes. Results: A total of 824 patients (median [range] age at diagnosis 7.5 [0-18.9] years; 361 girls [44%]) were assessed, including 335 children with a hematological neoplasm (41%) and 489 (59%) with a solid tumor. In 71 of 824 children (8.6%), a CPS was identified, of which most (96%) were identified by a phenotype-driven approach. Down syndrome and neurofibromatosis type 1 were the most common CPSs diagnosed. In 42 of 71 patients (59%), a CPS was identified after these children developed a neoplasm. The specific type of neoplasm was the most frequent indicator for genetic testing, whereas family history played a minor role. Conclusions and Relevance: In this cohort study of children with a neoplasm, the prevalence of CPSs identified by a phenotype-driven approach was 8.6%. The diagnostic approach for identifying CPSs is currently shifting toward a genotype-first approach. Future studies are needed to determine the diagnostic value, as well as possible disadvantages of CPS gene sequencing among all children with cancer compared with the phenotype-driven approach. This cohort study examines a Dutch national children's cancer center's experience in diagnosing cancer predisposition syndromes before introducing routine next-generation genetic sequencing.
- Subjects
NETHERLANDS; TUMOR risk factors; SEQUENCE analysis; DOWN syndrome; GENETIC testing; RETROSPECTIVE studies; OPHTHALMOLOGISTS; RISK assessment; CANCER patients; DISEASE susceptibility; DESCRIPTIVE statistics; RESEARCH funding; NEUROFIBROMATOSIS; PHENOTYPES; ONCOLOGISTS; CHILDREN
- Publication
JAMA Network Open, 2023, Vol 6, Issue 1, pe2254157
- ISSN
2574-3805
- Publication type
Article
- DOI
10.1001/jamanetworkopen.2022.54157