Segregation analysis of the BRCA2 c.9227G>T variant in multiple families suggests a pathogenic role in breast and ovarian cancer predisposition.
Sci Rep
; 10(1): 13987, 2020 08 19.
Article
de En
| MEDLINE
| ID: mdl-32814805
ABSTRACT
Classification of variants in the BRCA1 and BRCA2 genes has a major impact on the clinical management of subjects at high risk for breast and ovarian cancer. The identification of a pathogenic variant allows for early detection/prevention strategies in healthy carriers as well as targeted treatments in patients affected by BRCA-associated tumors. The BRCA2 c.9227G>T p.(Gly3076Val) variant recurs in families from Northeast Italy and is rarely reported in international databases. This variant substitutes the evolutionary invariant glycine 3076 with a valine in the DNA binding domain of the BRCA2 protein, thus suggesting a high probability of pathogenicity. We analysed clinical and genealogic data of carriers from 15 breast/ovarian cancer families in whom no other pathogenic variants were detected. The variant was shown to co-segregate with breast and ovarian cancer in the most informative families. Combined segregation data led to a likelihood ratio of 81,5271 of pathogenicity vs. neutrality. We conclude that c.9227G>T is a BRCA2 pathogenic variant that recurs in Northeast Italy. It can now be safely used for the predictive testing of healthy family members to guide preventive surgery and/or early tumor detection strategies, as well as for PARP inhibitors treatments in patients with BRCA2-associated tumors.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Tumeurs de l'ovaire
/
Tumeurs du sein
/
Prédisposition génétique à une maladie
/
Polymorphisme de nucléotide simple
/
Protéine BRCA2
Type d'étude:
Diagnostic_studies
/
Prognostic_studies
/
Screening_studies
Limites:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Langue:
En
Journal:
Sci Rep
Année:
2020
Type de document:
Article
Pays d'affiliation:
Italie