Landscape of germline BRCA1/BRCA2 variants in breast and ovarian cancer in Peru

Yomali Ferreyra; Gina Rosas; Alicia M Cock-Rada; Jhajaira Araujo; Leny Bravo; Franco Doimi; Jhoysi Casas; María de Los Ángeles Clavo; Joseph A Pinto; Carolina Belmar-López

doi:10.3389/fonc.2023.1227864

Landscape of germline BRCA1/BRCA2 variants in breast and ovarian cancer in Peru

Front Oncol. 2023 Aug 17:13:1227864. doi: 10.3389/fonc.2023.1227864. eCollection 2023.

Authors

Affiliations

¹ Departamento de Bioingeniería, Universidad de Ingenieria y Tecnología, Lima, Peru.
² Departamento de Patología, Insituto Nacional de Enfermedades Neoplásicas, Lima, Peru.
³ Departmento de Oncología Médica, Instituto de Cancerología Las Américas - Auna, Medellín, Colombia.
⁴ Centro de Investigación Básicas y traslacional, Auna Ideas, Lima, Peru.
⁵ Escuela Profesional de Medicina Humana-Filial Ica, Universidad Privada San Juan Bautista, Ica, Peru.
⁶ Oncogenomics, Auna, Lima, Peru.
⁷ Facultad de Medicina Humana, Universidad Nacional San Luis Gonzaga, Ica, Peru.

Abstract

Background: There is an increasing amount of data from Latin America on the characterization of BRCA variants; however, there is limited information from Peru. We conducted a retrospective study to describe germline pathogenic/likely pathogenic(P/LP) variants and variants of uncertain/unknown significance (VUS) in the BRCA1 and BRCA2 genes in Peru, in patients with breast and ovarian cancer, candidates for treatment with poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors.

Methods: The patients were evaluated during the period 2019-2021. Genomic DNA was isolated from peripheral blood samples and targeted sequencing was performed using the Ampliseq BRCA panel. Genetic variant interpretation was carried out in accordance with the recommendations of the American College of Medical Genetics and ClinVar. During this period, 525 patients (143 with breast cancer and 382 with ovarian cancer) were studied.

Results: We found that 14.7% (21/143) of breast cancer patients and 20.7% (79/382) of ovarian cancer patients were carriers of P/LP variants in BRCA1/2. The most frequent pathogenic variants detected in BRCA1 were c.2105dupT (BIC: 2224insT, n=12, 18.75%), c.68_69delAG (BIC: 185delAG, n=6, 9.38%), c.140G>T and c.815_824dupAGCCATGTGG (n=5, 7.81%), while in BRCA2 were c.8023A>G (n=6, 16.67%), c.6024dupG (BIC: 6252insG, n=4, 11.11%), and c.9235delG (BIC: 9463delG, n=3, 8.33%). Regarding VUS, we found that 6.99% (10/143) of breast cancer patients and 7.33% (28/382) of ovarian cancer patients were carriers of a VUS in BRCA1/2. For BRCA1, the most frequent VUS was c.93C>G (n=2), and for BRCA2, c.5465A>T (n=4), c.3101T>C (n=3), c.205C>A and c.437T>C (n=2).

Conclusion: We found a frequency of 14.7% germline mutations in breast cancer patients and 20.7% in ovarian cancer patients. The most recurrent mutations were BRCA1 c.2105dupT and BRCA2 c.8023A>G. We found that BRCA2 c.8023A>G, c.6024dupG, and c.9235delG were not previously reported in Peruvian patients. BRCA1 c.2344dupA is a novel mutation that has not been previously reported in any database. The frequency of VUS in our cohort was 7.2%.

Keywords: BRCA1; BRCA2; breast cancer; germline mutation; ovarian cancer.