Browse by author
Lookup NU author(s): Professor Deborah TweddleORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2026 The AuthorsBackground: Neuroblastoma and Wilms tumour (WT) are common childhood embryonal malignancies. Germline 2p24 duplication has been reported in several cases of neuroblastoma and WT, either as part of a larger 2p duplication or as a microduplication involving just 2p24.3. Although the larger duplications involve many genes, including ALK, the microduplications have been localised to a region including MYCN and DDX1. Methods: We analysed Whole Genome Sequence data from adults and children sequenced for various indications. We utilised a workflow to extract structural and copy number variants, filtered to include duplications or gains of 2 kb–20 Mb, including these loci, followed by manual inspection in IGV. Associations were assessed using Fisher's exact test. Penetrance was estimated by Bayesian calculation of the conditional probability of disease. Findings: Among 113,431 genomes, there were 6 participants with a microduplication that included the MYCN locus. Of these, two had a diagnosis of WT and one of neuroblastoma. The 2p24.3 microduplication was therefore identified in 3/197 with a definite history of WT/neuroblastoma and 3/113,234 without such a history (p < 0.0001). Penetrance is estimated to be 13%. Twelve participants were identified with a 2p24.3 microduplication that included the DDX1 locus but not MYCN, none of whom received a diagnosis of a childhood embryonal tumour. Interpretation: We have shown that 2p24.3 microduplications that include MYCN predispose to childhood embryonal tumours and should be routinely assessed when WT or neuroblastoma predisposition is suspected. We have also shown that there does not appear to be any increased incidence of childhood tumours when DDX1 alone is duplicated. Funding: UCL Great Ormond Street Institute of Child Health Child Health Research CIO PhD Studentship, Brain Tumour Charity, Children with Cancer UK, Great Ormond Street Hospital Children's Charity, Olivia Hodson Cancer Fund, Cancer Research UK and the National Institute for Health Research.
Author(s): Taylor CA, May P, Stone TJ, Ahmed M, Chowdhury T, Tweddle DA, Wilson S, Hanscombe K, Hutchinson JC, Pickles JC, Sebire NJ, Jacques TS
Publication type: Article
Publication status: Published
Journal: eBioMedicine
Year: 2026
Volume: 124
Print publication date: 01/02/2026
Online publication date: 31/01/2026
Acceptance date: 09/01/2026
Date deposited: 09/02/2026
ISSN (electronic): 2352-3964
Publisher: Elsevier B.V.
URL: https://doi.org/10.1016/j.ebiom.2026.106132
DOI: 10.1016/j.ebiom.2026.106132
Data Access Statement: Research on the de-identified patient data used in this publication can be carried out in the Genomics England Research Environment subject to a collaborative agreement that adheres to patient-led governance. All interested readers will be able to access the data in the same manner that the authors accessed the data. For more information about accessing the data, interested readers may contact research-network@ genomicsengland.co.uk or access the relevant information on the Genomics England website: https://www.genomicsengland.co.uk/ research.
Altmetrics provided by Altmetric
