Identification of Variants (rs11571707, rs144848, and rs11571769) in the BRCA2 Gene Associated with Hereditary Breast Cancer in Indigenous Populations of the Brazilian Amazon

Estimates show that 5–10% of breast cancer cases are hereditary, caused by genetic variants in autosomal dominant genes; of these, 16% are due to germline mutations in the BRCA1 and BRCA2 genes. The comprehension of the mutation profile of these genes in the Brazilian population, particularly in Amazonian Amerindian groups, is scarce. We investigated fifteen polymorphisms in the BRCA1 and BRCA2 genes in Amazonian Amerindians and compared the results with the findings of global populations publicly available in the 1000 Genomes Project database. Our study shows that three variants (rs11571769, rs144848, and rs11571707) of the BRCA2 gene, commonly associated with hereditary breast cancer, had a significantly higher allele frequency in the Amazonian Amerindian individuals in comparison with the African, American, European, and Asian groups analyzed. These data outline the singular genetic profiles of the indigenous population from the Brazilian Amazon region. The knowledge about BRCA1 and BRCA2 variants is critical to establish public policies for hereditary breast cancer screening in Amerindian groups and populations admixed with them, such as the Brazilian population.

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MUTATIONS IN BRCA1 AND BRCA2 GENES AS A CAUSE OF HEREDITARY BREAST CANCER

The Bulletin of Contemporary Clinical Medicine ◽

10.20969/vskm.2020.13(4).39-43 ◽

2020 ◽

Vol 13 (4) ◽

pp. 39-43

Author(s):

REGINA R. GIMAEVA ◽

◽

ELENA A. KUPRIYANOVA ◽

DENIS I. GABELKO ◽

◽

...

Keyword(s):

Breast Cancer ◽

Hereditary Breast Cancer ◽

Brca1 And Brca2 ◽

Brca1 And Brca2 Genes

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Germline promoter hypermethylation in BRCA1 and BRCA2 genes is not present in hereditary breast cancer patients

Clinical & Translational Oncology ◽

10.1007/s12094-018-1837-0 ◽

2018 ◽

Vol 20 (9) ◽

pp. 1226-1231 ◽

Cited By ~ 4

Author(s):

M. Rodríguez-Balada ◽

B. Roig ◽

M. Melé ◽

M. Salvat ◽

L. Martorell ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Hereditary Breast Cancer ◽

Promoter Hypermethylation ◽

Breast Cancer Patients ◽

Brca1 And Brca2 ◽

Brca1 And Brca2 Genes

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Hereditary breast cancer – a spectrum of pathogenic mutations and unknown variants of BRCA1 and BRCA2 genes in the Czech Republic: efficiency of testing and clinical follow-up

Breast Cancer Research ◽

10.1186/bcr1093 ◽

2005 ◽

Vol 7 (S2) ◽

Author(s):

L Foretova ◽

M Lukesova ◽

P Vasickova ◽

M Navratilova ◽

H Pavlu ◽

...

Keyword(s):

Breast Cancer ◽

Czech Republic ◽

Hereditary Breast Cancer ◽

Brca1 And Brca2 ◽

The Czech Republic ◽

Pathogenic Mutations ◽

Brca1 And Brca2 Genes

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Characteristics of BRCA-associated breast cancer in the population of the Russian Federation

Bulletin of Russian State Medical University ◽

10.24075/brsmu.2021.006 ◽

2021 ◽

Author(s):

EI Novikova ◽

EA Kudinova ◽

VK Bozhenko ◽

VA Solodkiy

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Russian Federation ◽

False Negative ◽

Brca2 Gene ◽

Breast Cancer Patients ◽

Brca1 And Brca2 ◽

Coding Regions ◽

Brca1 And Brca2 Genes ◽

The Russian Federation

"Standard" diagnostic panels allow identification of only a few of BRCA1 and BRCA2 gene mutations most common in a population. Therefore, tests relying on such panels may return false negative results, since the coding regions of these genes may have other defects. For breast cancer (BC) patients, false negative test results may translate into selection of inadequate therapy by their doctors. This study aimed to identify the features of BRCA-associated breast cancer in the population of the Russian Federation. The study included breast cancer patients (n = 4440). At the first stage, all patients were screened for the eight most common BRCA1 and BRCA2 genes mutations with the help of real-time PCR. Next, patients that exhibited clinical signs of a hereditary disease (CSHD) in the absence of common mutations (n = 290) had the entire coding regions of BRCA1 and BRCA2 genes studied with next generation sequencing (NGS). "Standard" mutations in the BRCA1 and BRCA2 genes were identified in 169 (3.8%) cases. In the CSHD group, such mutations were revealed in 15.4% of cases. NGS uncovered 33 rare pathogenic BRCA1 and BRCA2 gene mutations in 40 out of 290 breast cancer patients (13.8%). It was concluded that among the residents of the Russian Federation, the range of pathogenic variants of BRCA-associated breast cancer is wide, and it stretches beyond the mutations considered by the "standard" diagnostic panels. Analysis of the entire coding regions of BRCA1 and BRCA2 genes allows increasing efficiency of detection of germline mutations in breast cancer patients at least twofold.

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Double heterozygous pathogenic variants in the BRCA1 and BRCA2 genes in a patient with bilateral metachronous breast cancer: a case report

10.21203/rs.3.rs-412077/v1 ◽

2021 ◽

Author(s):

Alejandra Mampel ◽

Mayra L Sottile ◽

Silvina Denita-Juarez ◽

Ana Lía Vargas ◽

Laura M Vargas-Roig

Keyword(s):

Breast Cancer ◽

Bilateral Breast Cancer ◽

Brca2 Gene ◽

Cancer Case ◽

Brca1 And Brca2 ◽

Pathogenic Variants ◽

First Case ◽

Gene Panel Testing ◽

Brca1 And Brca2 Genes ◽

Double Heterozygosity

Abstract BackgroundDouble heterozygosity pathogenic variants in BRCA1 and BRCA2 genes are a very rare finding, particularly in non-Ashkenazi individuals. We described the first case of double heterozygosity variants in a non-Ashkenazi Argentinean woman with metachronous bilateral breast cancer. Case presentationThe proband is a 65-year-old female diagnosed with invasive ductal carcinoma in the left breast at 45 years old and invasive carcinoma in the right breast at 65 years old. She underwent a multi-gene panel testing indicating the presence of two concurrent heterozygous germline deleterious variants in BRCA1 (c.4201C>T), and BRCA2 (c.5146_5149del) genes. The patient’s son (40 years-old) was found to have the inherited pathogenic variant in BRCA2 gene. ConclusionThere are few reports of double heterozygosity variants in BRCA1 and BRCA2 genes in Latin America. The two pathogenic variants identified in our patient have not been described together so far.

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Hereditary breast cancer: Pathobiology, prognosis, and BRCA1 and BRCA2 gene linkage

Cancer ◽

10.1002/(sici)1097-0142(19960215)77:4<697::aid-cncr16>3.0.co;2-w ◽

1996 ◽

Vol 77 (4) ◽

pp. 697-709 ◽

Cited By ~ 316

Author(s):

Joseph N. Marcus ◽

Patrice Watson ◽

David L. Page ◽

Steven A. Narod ◽

Gilbert M. Lenoir ◽

...

Keyword(s):

Breast Cancer ◽

Hereditary Breast Cancer ◽

Brca2 Gene ◽

Brca1 And Brca2 ◽

Gene Linkage

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Contribution of BRCA1 and BRCA2 mutations to breast cancer in Tunisia

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e22191 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e22191-e22191

Author(s):

T. Wafa

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Hereditary Breast Cancer ◽

Brca2 Mutation ◽

Brca2 Gene ◽

Brca1 Gene ◽

Deleterious Mutations ◽

Brca1 And Brca2 ◽

Frameshift Mutations ◽

History Of

e22191 Background: Hereditary breast cancer accounts for 3–8% of all breast cancers. It was recently estimated that a combination of BRCA1 and BRCA2 genes mutations is responsible for 30% of hereditary breast cancer cases. Methods: To investigate the prevalence of BRCA1 and BRCA2 gene mutations in breast cancer patients with affected relatives in Tunisia, 36 patients who had at least one first degree relative affected with breast and/or ovarian cancer were analysed. Thirty three patients are suggestive of BRCA1 mutation and 3 are suggestive of BRCA2 mutation. Results: Four mutations in BRCA1 gene were described among which, one novel splice site mutation (330 dupA) and 3 frameshift mutations including the 4160 delAG, the 2789 delG and the 5385 insC. Our study is the first to describe the 5385 insC mutation which was described only among Jewish Ashkenazi population. Two frameshift mutations (1537 del4 and 5909 insA) were screened in BRCA2 gene. Nineteen percent (7/36) of the familial cases were altered on BRCA1 or BRCA2 genes with deleterious mutations at heterozygous state and 55% (20/36) by mutation with uncertain value (UV) or by single nucleotide polymorphisms (SNPs). Conclusions: Almost all the cases mutated by deleterious mutations on BRCA1 gene reported a family history of breast and/or ovarian cancer in the index case or in their relatives. On the contrary, patients with an UV mutation or SNPs have no history of ovarian cancer in their corresponding families. Our data are the first to contribute to information on mutation spectrum of BRCA genes and offer a recommended screening mode for clinical genetic testing policy in Tunisia. No significant financial relationships to disclose.

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