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

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.

The occurrence of ovarian cancer in the population of urban and rural women, BRCA1 and BRCA2 genes mutation testing and the general rules on the patient’s consent to treatment

Introduction. The BRCA1 and BRCA2 genes belong to suppressor genes that control the mechanisms of repairing various damages of the DNA double helix, regulate cell division, and the cell cycle. Mutations within these genes are associated with the hereditary ovarian and breast cancers. Aim. Assessment of the frequency of testing BRCA1 and BRCA2 gene mutation in the population of women living in urban and rural environments with diagnosed ovarian cancer. Material and methods. The study was conducted among 300 women seeking treatment or consulting a doctor from the Wielkopolska Oncology Center in Poznań, and patients treated in a home hospice in the Rawicz district in Wielkopolska province over the period 2016-2018. Results. Among the respondents, the most were women aged from 36 to 40 (53.3%). The age of developing ovarian cancer for the women from cities is between 41 and 45. In the vast majority of women, i.e. 247 (82.3%), epithelial cancer was diagnosed. A marker that could indicate ovarian cancer, i.e. CA 125 antigen, was determined in more than half of 165 (55.0%). However, only in a few cases, in a total of 25 (8.3%) patients a test confirming the presence of BRCA1 and BRCA2 gene mutation was performed. Conclusions. The possibility of testing for BRCA1 and BRCA2 gene mutation in all sick women and their closest family should be considered. Regardless of the age of women, it is important to raise awareness of the risk of ovarian cancer, encourage them to keep regular medical appointments, and perform diagnostic tests.

Characteristics of BRCA-associated breast cancer in the population of 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.

Screening for mutations in BRCA1 and BRCA2 genes and related perspectives for the healthcare system

In the article there were looked some aspects of the knowledge regarding mutations in BRCA1 BRCA2 genes that have been accumulated since the first report on role of these genes in the development of breast and ovarian cancer. Most of them have practical worth related to the detection of mutations, as well as the prevention and treatment of associated ovarian cancer (the article focuses specifically on ovarian cancer, conditioned to relatively less amount of information on this pathology). There has been paid attention to the rational assignment of a genetic test on the presence of mutations in BRCA genes.Keywords: ovarian cancer, mutations in BRCA1 BRCA2 genes, screening of the presence mutations in BRCA1 BRCA2 genes.

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.