A de novo germline pathogenic BRCA1 variant identified following an osteosarcoma pangenomic molecular analysis.
de novo
BRCA1
Osteosarcoma
Tumor sequencing
Whole genome
Journal
Familial cancer
ISSN: 1573-7292
Titre abrégé: Fam Cancer
Pays: Netherlands
ID NLM: 100898211
Informations de publication
Date de publication:
19 May 2024
19 May 2024
Historique:
received:
21
01
2024
accepted:
17
04
2024
medline:
20
5
2024
pubmed:
20
5
2024
entrez:
19
5
2024
Statut:
aheadofprint
Résumé
De novo germline pathogenic variants (gPV) of the BReast CAncer 1 (BRCA1) gene are very rare. Only a few have been described up to date, usually in patients with a history of ovarian or breast cancer. Here, we report the first case of an incidental de novo BRCA1 germline pathogenic variant which was identified within the framework of the Plan France Médecine Génomique (PFMG) 2025 French national tumor sequencing program. The proband was a 29-year-old man diagnosed with metastatic osteosarcoma. Tumor whole exome sequencing identified a BRCA1 c.3756_3759del p.(Ser1253Argfs*10) pathogenic variant without loss-of-heterozygosity. A low genomic instability score and the absence of single base substitution signatures of homologous recombination deficiency suggested that the BRCA1 variant was not driver in the osteosarcoma tumorigenesis. Germline whole genome sequencing asserted the germline nature of this variant, with a 36% allele frequency, suggesting a mosaicism caused by a post-zygotic mutational event. The proband's family (parents and siblings) were not carriers of this variant confirming the de novo occurrence. Tumor sequencing programs like the French PFMG 2025 have been implemented worldwide and may help identify new gPV, including de novo variants.
Identifiants
pubmed: 38763984
doi: 10.1007/s10689-024-00393-0
pii: 10.1007/s10689-024-00393-0
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature B.V.
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