Copy number variations contribute to malignant tumor development in children with serious birth defects.
birth defects
copy number variations
pediatric cancers
whole‐genome sequencing
Journal
Molecular oncology
ISSN: 1878-0261
Titre abrégé: Mol Oncol
Pays: United States
ID NLM: 101308230
Informations de publication
Date de publication:
14 Aug 2024
14 Aug 2024
Historique:
revised:
01
07
2024
received:
01
03
2024
accepted:
30
07
2024
medline:
14
8
2024
pubmed:
14
8
2024
entrez:
14
8
2024
Statut:
aheadofprint
Résumé
There are two key signatures of pediatric cancers: (a) higher prevalence of germline alterations and (b) heterogeneity in alteration types. Recent population-based assessments have demonstrated that children with birth defects (BDs) are more likely to develop cancer even without chromosomal anomalies; therefore, explorations of genetic alterations in children with BDs and cancers could provide new insights into the underlying mechanisms for pediatric tumor development. We performed whole-genome sequencing (WGS) on blood-derived DNA for 1556 individuals without chromosomal anomalies, including 454 BD probands with at least one type of malignant tumor, 757 cancer-free children with BDs, and 345 healthy individuals, focusing on copy number variation (CNV) analysis. Roughly half of the children with BD-cancer have CNVs that are not identified in BD-only/healthy individuals, and CNVs are not evenly distributed among these patients. Strong heterogeneity was observed, with a limited number of cancer predisposition genes containing CNVs in more than three patients. Moreover, functional enrichments of genes with CNVs showed that dozens of patients have variations related to the same biological pathways, such as deletions of genes with neurological functions and duplications of immune response genes. Phenotype clustering uncovered recurrences of patients with sarcoma: A notable enrichment was observed involving non-coding RNA regulators, showing strong signals related to growth and cancer regulations in functional analysis. In conclusion, we conducted one of the first genomic studies exploring the impact of CNVs on cancer development in children with BDs, unveiling new insights into the underlying biological processes.
Identifiants
pubmed: 39140252
doi: 10.1002/1878-0261.13718
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Children's Hospital of Philadelphia
Organisme : Common Fund of the Office of the Director of the National Institutes of Health
Informations de copyright
© 2024 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
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