The coexistence of a BRCA2 germline and a DICER1 somatic variant in two first-degree cousins suggests their potential synergic effect.
BRCA genes
DICER1
Cancer predisposition syndrome
Cystic nephroma
Pediatric oncology
Primary intracranial DICER1-mutated sarcoma
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
13 Sep 2024
13 Sep 2024
Historique:
received:
17
05
2024
accepted:
29
08
2024
medline:
14
9
2024
pubmed:
14
9
2024
entrez:
13
9
2024
Statut:
epublish
Résumé
Cancer predisposition syndromes are recognized in about 10% of pediatric malignancies with several genes specifically involved in a subset of pediatric tumors such as DICER1, in pleuropulmonary blastoma, cystic nephroma, and brain sarcomas. By contrast, the role of BRCA1/2 in pediatric cancer predisposition is still under investigation. We present two cases of young first-degree cousins, both carrying a germline BRCA2 variant and developing tumors characterized by somatic DICER1 mutations. Patient 1 presented with a cystic nephroma harboring a somatic DICER1 variant (p.Asp1810Tyr), while patient 2 had a primary intracranial DICER1-mutated sarcoma showing a distinct somatic DICER1 variant (p.Asp1709Glu) as well as biallelic inactivation of TP53 (p.Val173Leu, VAF 91%) and APC (p.Ile1307Lys, VAF 95%) and a pathogenic variant in KRAS (p.Gln61His). Both patients carried the same germline BRCA2 variant (p.Arg2842Cys) of unknown significance. The same variant was found in the mother of patient 2 and in the father of patient 1, who are siblings. A homologous recombination deficiency signature was not identified in any of the two tumors, possibly suggesting a reduction of BRCA2 activity. The association of BRCA2 and DICER1 variants in our cases hints at a potential cooperative role in cancer pathogenesis. Further studies are warranted to elucidate the interplay between BRCA1/2 and DICER1 variants and their implications for cancer predisposition and treatment in pediatric patients.
Identifiants
pubmed: 39271738
doi: 10.1038/s41598-024-71667-x
pii: 10.1038/s41598-024-71667-x
doi:
Substances chimiques
DEAD-box RNA Helicases
EC 3.6.4.13
DICER1 protein, human
EC 3.1.26.3
Ribonuclease III
EC 3.1.26.3
BRCA2 Protein
0
BRCA2 protein, human
0
Types de publication
Journal Article
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
21435Informations de copyright
© 2024. The Author(s).
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