1. Complex structural variation is prevalent and highly pathogenic in pediatric solid tumors.
- Author
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van Belzen IAEM, van Tuil M, Badloe S, Janse A, Verwiel ETP, Santoso M, de Vos S, Baker-Hernandez J, Kerstens HHD, Solleveld-Westerink N, Meister MT, Drost J, van den Heuvel-Eibrink MM, Merks JHM, Molenaar JJ, Peng WC, Tops BBJ, Holstege FCP, Kemmeren P, and Hehir-Kwa JY
- Subjects
- Humans, Child, DNA Copy Number Variations, Genomic Structural Variation genetics, Female, Male, Child, Preschool, Chromothripsis, Neoplasms genetics, Neoplasms epidemiology
- Abstract
In pediatric cancer, structural variants (SVs) and copy-number alterations contribute to cancer initiation as well as progression, thereby aiding diagnosis and treatment stratification. Although suggested to be of importance, the prevalence and biological relevance of complex genomic rearrangements (CGRs) across pediatric solid tumors is largely unexplored. In a cohort of 120 primary tumors, we systematically characterized patterns of extrachromosomal DNA, chromoplexy, and chromothripsis across five pediatric solid cancer types. CGRs were identified in 56 tumors (47%), and in 42 of these tumors, CGRs affect cancer driver genes or result in unfavorable chromosomal alterations. This demonstrates that CGRs are prevalent and pathogenic in pediatric solid tumors and suggests that selection likely contributes to the structural variation landscape. Moreover, carrying CGRs is associated with more adverse clinical events. Our study highlights the potential for CGRs to be incorporated in risk stratification or exploited for targeted treatments., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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