Genomic instability in congenital lung malformations in children.
5p15.33
Congenital lung malformations
Genomic instability
Lung tumors
Methylation
TERT oncogene
Whole genome
Journal
Pediatric surgery international
ISSN: 1437-9813
Titre abrégé: Pediatr Surg Int
Pays: Germany
ID NLM: 8609169
Informations de publication
Date de publication:
05 Sep 2024
05 Sep 2024
Historique:
accepted:
31
08
2024
medline:
6
9
2024
pubmed:
6
9
2024
entrez:
5
9
2024
Statut:
epublish
Résumé
To study the biological relationship between congenital lung malformations (CLMs) and malignancy. Biopsies of 12 CPAMs, 6 intralobar sequestrations and 2 extralobar sequestrations were analyzed through whole-genome sequencing. Blood samples from 10 patients were used to confirm or exclude somatic mosaicism. Putative somatic Single Nucleotide Variants (SNVs) were called for each malformed sample with a Panel of Normals built with control DNA samples extracted from blood. The variants were subsequently confirmed by Sanger sequencing and searched, whenever possible, in the blood samples of patients. All CLMs but one presented a signature of genomic instability by means of multiple clusters of cells with gene mutations. Seven tumor transformation-related SNVs were detected in 6/20 congenital lung malformations. Four very rare in the general population SNVs were found in a region previously linked to lung cancer in 5p15.33, upstream of TERT oncogene. Furthermore, we identified missense genetic variants, whose tumorigenic role is well known, in the RET, FANCA and MET genes. Genomic instability in 95% of CLMs and genetic variants linked to tumor development in 30% of them, regardless of histopathology, are predisposing factors to malignancy, that combined with exposure to carcinogens, might trigger the development of malignancy and explain the association between CLMs and lung cancer.
Identifiants
pubmed: 39237666
doi: 10.1007/s00383-024-05835-5
pii: 10.1007/s00383-024-05835-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
248Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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