Landscape of germline BRCA1/BRCA2 variants in breast and ovarian cancer in Peru
BackgroundThere 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 signific...
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1227864/full |
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| author | 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 Carolina Belmar-López |
| author_facet | 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 Carolina Belmar-López |
| author_sort | Yomali Ferreyra |
| collection | DOAJ |
| description | BackgroundThere 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.MethodsThe 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. ResultsWe 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). ConclusionWe 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%. |
| first_indexed | 2024-03-12T14:25:19Z |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-12T14:25:19Z |
| publishDate | 2023-08-01 |
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| series | Frontiers in Oncology |
| spelling | doaj.art-7892300d480847c3828bd1ef1dd59ff22023-08-18T07:47:04ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-08-011310.3389/fonc.2023.12278641227864Landscape of germline BRCA1/BRCA2 variants in breast and ovarian cancer in PeruYomali Ferreyra0Gina Rosas1Alicia M. Cock-Rada2Jhajaira Araujo3Leny Bravo4Franco Doimi5Jhoysi Casas6María de los Ángeles Clavo7Joseph A. Pinto8Carolina Belmar-López9Carolina Belmar-López10Departamento de Bioingeniería, Universidad de Ingenieria y Tecnología, Lima, PeruDepartamento de Patología, Insituto Nacional de Enfermedades Neoplásicas, Lima, PeruDepartmento de Oncología Médica, Instituto de Cancerología Las Américas - Auna, Medellín, ColombiaCentro de Investigación Básicas y traslacional, Auna Ideas, Lima, PeruEscuela Profesional de Medicina Humana-Filial Ica, Universidad Privada San Juan Bautista, Ica, PeruOncogenomics, Auna, Lima, PeruOncogenomics, Auna, Lima, PeruFacultad de Medicina Humana, Universidad Nacional San Luis Gonzaga, Ica, PeruCentro de Investigación Básicas y traslacional, Auna Ideas, Lima, PeruEscuela Profesional de Medicina Humana-Filial Ica, Universidad Privada San Juan Bautista, Ica, PeruOncogenomics, Auna, Lima, PeruBackgroundThere 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.MethodsThe 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. ResultsWe 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). ConclusionWe 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%.https://www.frontiersin.org/articles/10.3389/fonc.2023.1227864/fullbreast cancerovarian cancerBRCA1BRCA2germline mutation |
| spellingShingle | 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 Carolina Belmar-López Landscape of germline BRCA1/BRCA2 variants in breast and ovarian cancer in Peru Frontiers in Oncology breast cancer ovarian cancer BRCA1 BRCA2 germline mutation |
| title | Landscape of germline BRCA1/BRCA2 variants in breast and ovarian cancer in Peru |
| title_full | Landscape of germline BRCA1/BRCA2 variants in breast and ovarian cancer in Peru |
| title_fullStr | Landscape of germline BRCA1/BRCA2 variants in breast and ovarian cancer in Peru |
| title_full_unstemmed | Landscape of germline BRCA1/BRCA2 variants in breast and ovarian cancer in Peru |
| title_short | Landscape of germline BRCA1/BRCA2 variants in breast and ovarian cancer in Peru |
| title_sort | landscape of germline brca1 brca2 variants in breast and ovarian cancer in peru |
| topic | breast cancer ovarian cancer BRCA1 BRCA2 germline mutation |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1227864/full |
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