TY - JOUR
T1 - Assessment of Cancer Predisposition Syndromes in a National Cohort of Children With a Neoplasm
AU - Bakhuizen, Jette J.
AU - Hopman, Saskia M. J.
AU - Bosscha, Machteld I.
AU - Dommering, Charlotte J.
AU - van den Heuvel-Eibrink, Marry M.
AU - Hol, Janna A.
AU - Kester, Lennart A.
AU - Koudijs, Marco J.
AU - Langenberg, Karin P. S.
AU - Loeffen, Jan L. C.
AU - van der Lugt, Jasper
AU - Moll, Annette C.
AU - van Noesel, Max M.
AU - Smetsers, Stephanie E.
AU - de Vos-Kerkhof, Evelien
AU - Merks, Johannes H. M.
AU - Kuiper, Roland P.
AU - Jongmans, Marjolijn C. J.
N1 - Funding Information: This work was supported by the Dutch Children Cancer-free Foundation (KIKA) grant 355. Publisher Copyright: © 2023 American Medical Association. All rights reserved.
PY - 2023/2/3
Y1 - 2023/2/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85147457887&partnerID=8YFLogxK
U2 - https://doi.org/10.1001/jamanetworkopen.2022.54157
DO - https://doi.org/10.1001/jamanetworkopen.2022.54157
M3 - Article
C2 - 36735256
SN - 2574-3805
VL - 6
SP - e2254157
JO - JAMA network open
JF - JAMA network open
IS - 2
M1 - e2254157
ER -