Caracterização epidemiológica e fenotípica da variante c.9382C>T (p.Arg3128Ter) no gene BRCA2 identificada em onze famílias num hospital do Norte de Portugal

Abstract

Introduction: The BRCA2 c.9382C>T (p.Arg3128Ter) variant is classified as pathogenic and is described in GnomAD at a frequency of 0.0021%. From the total of families with BRCA2 variants identified at Centro Hospitalar Universitário de São João, this is the second most frequent. The aim of this study is to characterize 11 families carrying this variant in the BRCA2 gene, as to their geographical distribution and the phenotypic characteristics expressed in the carriers. Material and Methods: Descriptive observational study, based on the review of clinical processes of individuals carrying the BRCA2 c.9382C>T variant, identified in the Oncogenetic Clinic of Centro Hospitalar Universitário de São João. Results: Eleven portuguese families were identified with the BRCA2 c.9382C>T variant, from Barcelos (n=5), Madeira (n=3), Braga (n=2) and Vila do Conde (n=1). From the 31 mutation carriers, 48.4% developed cancer, most of them breast cancer (n=11). The mean age at the first diagnosis was 40.5 ± 7.1 years. The most frequent histological type was the invasive carcinoma of no special type (n=6). All invasive carcinomas expressed hormonal receptors (n=9). Discussion: We found a number of families carrying the BRCA2 c.9382C>T variant higher than expected, given its frequency worldwide. Most patients developed breast cancer with histopathological characteristics consistent with that described in the literature for cancer associated with BRCA2 gene mutation. Conclusion: The recurrence of this variant may be related to a founding effect of the mutation in Portugal. We suggest nine microsatellite markers for a future haplotyping of these families.