Background: Breast cancer is one of the most prevalent malignancies in the world. In Peru, breast cancer is the second cause of death among women. Five to ten percent of patients present a high genetic predisposition due to BRCA1 and BRCA2 germline mutations. Methods: We performed a comprehensive analysis of BRCA1 and BRCA2 genes by Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) to detect large rearrangements in patients from 18 families, which met the criteria for hereditary breast cancer. Results: In this series, we found four pathogenic mutations, three previously reported (BRCA1: c.302-1G>C and c.815_824dup10; BRCA2: c.5946delT) and a duplication of adenines in exon 15 in BRCA1 gene (c.4647_4648dupAA, ClinVar SCV000256598.1). We also found two exonic and four intronic variants of unknown significance and 28 polymorphic variants. Conclusion: This is the first report to determine the spectrum of mutations in the BRCA1/BRCA2 genes in Peruvian families selected by clinical and genetic criteria. The alteration rate in BRCA1/BRCA2 with proven pathogenic mutation was 22.2% (4 out 18) and this finding could be influenced by the reduced sample size or clinical criteria. In addition, we found three known BRCA1/BRCA2 mutations and a BRCA1 c.4647_4648dupAA as a novel pathogenic mutation.
Bibliographical noteFunding Information:
The authors are grateful for the patients and their family members for participating in this study. We thank Omar Caceres and Heiner Guio (Instituto Nacional de Salud) for support in sequencing procedures. This study was funded by research grants from the Facultad de Medicina de la Universidad de San Martın de Porres (Project E1001-2015048), FINCyT No. 138-PNICP-PIAP-2015, Oncosalud-AUNA, Instituto Nacional de Salud (Project: “Caracterizacion Molecular de Mutaciones Hereditarias en Familias con Historial de Cancer de Mama y Ovario”) and Origenetica SAC.
© 2017 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.
Copyright 2021 Elsevier B.V., All rights reserved.
- BRCA1 gene
- BRCA2 gene
- hereditary breast and ovarian cancer syndrome
- molecular analysis