Genomic instability in congenital lung malformations in children.
Pediatr Surg Int
; 40(1): 248, 2024 Sep 05.
Article
em En
| MEDLINE
| ID: mdl-39237666
ABSTRACT
PURPOSE:
To study the biological relationship between congenital lung malformations (CLMs) and malignancy.METHODS:
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.RESULTS:
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.CONCLUSIONS:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Instabilidade Genômica
Limite:
Adolescent
/
Child
/
Child, preschool
/
Female
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Humans
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Infant
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Male
/
Newborn
Idioma:
En
Revista:
Pediatr Surg Int
Assunto da revista:
PEDIATRIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Itália
País de publicação:
Alemanha