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

2021 ◽  
Vol 18 (1-2) ◽  
pp. 44-57
Author(s):  
Y. O. Tabaliuk ◽  
L. A. Rybchenko ◽  
B. T. Klimuk ◽  
S. V. Klymenko
Keyword(s):  
Ovarian Cancer ◽  
Genetic Test ◽  
Breast And Ovarian Cancer ◽  
Brca1 And Brca2 ◽  
Brca1 And Brca2 Genes ◽  
Prevention And Treatment ◽  
Cancer Mutations ◽  
Brca1 Brca2 ◽  
Detection Of Mutations

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.

scholarly journals Investigating the causal role of MRE11A p.E506* in breast and ovarian cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Islam E. Elkholi ◽  
Massimo Di Iorio ◽  
Somayyeh Fahiminiya ◽  
Suzanna L. Arcand ◽  
HyeRim Han ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Utility ◽  
Case Control Study ◽  
Genetic Test ◽  
Molecular Function ◽  
Breast And Ovarian Cancer ◽  
Increased Risk ◽  
Somatic Alterations ◽  
Control Study

AbstractThe nuclease MRE11A is often included in genetic test panels for hereditary breast and ovarian cancer (HBOC) due to its BRCA1-related molecular function in the DNA repair pathway. However, whether MRE11A is a true predisposition gene for HBOC is still questionable. We determined to investigate this notion by dissecting the molecular genetics of the c.1516G > T;p.E506* truncating MRE11A variant, that we pinpointed in two unrelated French-Canadian (FC) HBOC patients. We performed a case–control study for the variant in ~ 2500 breast, ovarian, and endometrial cancer patients from the founder FC population of Quebec. Furthermore, we looked for the presence of second somatic alterations in the MRE11A gene in the tumors of the carriers. In summary, these investigations suggested that the identified variant is not associated with an increased risk of developing breast or ovarian cancer. We finally performed a systematic review for all the previously reported MRE11A variants in breast and ovarian cancer. We found that MRE11A germline variants annotated as pathogenic on ClinVar often lacked evidence for such classification, hence misleading the clinical management for affected patients. In summary, our report suggests the lack of clinical utility of MRE11A testing in HBOC, at least in the White/Caucasian populations.

scholarly journals The spectrum of the most common BRCA1/BRCA2 mutations in Lithuanian high risk families

Genetika ◽  
2017 ◽  
Vol 49 (1) ◽  
pp. 43-50
Author(s):  
Danielius Serapinas ◽  
Marius Sukys ◽  
Agne Bartkeviciute ◽  
Diana Barkauskiene ◽  
Daiva Bartkeviciene
Keyword(s):  
Ovarian Cancer ◽  
High Risk ◽  
Brca2 Mutation ◽  
Health Science ◽  
University Hospital ◽  
Breast And Ovarian Cancer ◽  
Brca1 And Brca2 ◽  
Incidence And Mortality ◽  
Brca2 Mutations ◽  
Brca1 Brca2

Breast cancer is the neoplasm with the highest incidence and mortality among women in Lithuania. The aim of the study was to determine the mutational incidence in BRCA1 and BRCA2 genes in high-risk breast and/or ovarian cancer families. After written informed consent, 36 participants from Lithuanian health science university hospital provided a blood sample for genetic analysis. Molecular diagnostics was done for 6 BRCA1and BRCA2 mutations. From 36 tested subjects for BRCA1/BRCA2 mutations. Positive test for BRCA1/BRCA2 mutations test was found in 12 (33%) cases. Most common BRCA1 mutation was 5328insC - 6 (50%) cases, other mutations: 185delAG - 1 (8,3%), 300t>6(c61G) - 4 (33,3%), 4153 del A - 1 (8,3%). All mutations were BRCA1, but none of the women were positive for the analyzed BRCA2 mutation. The mean age when the cancer was diagnosed in BRCA1 mutations group was 40.40?3.39 comparing with the group without mutations - 43.29 ?2.52. Rates of BRCA1 and BRCA2 mutation testing are increasing in young women with breast and ovarian cancer. Detected mutations in BRCA1 contribute to up to one-third of the families with breast and ovarian cancer in Lithuania.

scholarly journals BARD1 Pathogenic Variants Are Associated with Triple-Negative Breast Cancer in a Spanish Hereditary Breast and Ovarian Cancer Cohort

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 150
Author(s):  
Paula Rofes ◽  
Jesús Del Valle ◽  
Sara Torres-Esquius ◽  
Lídia Feliubadaló ◽  
Agostina Stradella ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Triple Negative ◽  
Panel Analysis ◽  
Breast And Ovarian Cancer ◽  
Brca1 And Brca2 ◽  
Risk Gene ◽  
Pathogenic Variants ◽  
High Penetrance

Only a small fraction of hereditary breast and/or ovarian cancer (HBOC) cases are caused by germline variants in the high-penetrance breast cancer 1 and 2 genes (BRCA1 and BRCA2). BRCA1-associated ring domain 1 (BARD1), nuclear partner of BRCA1, has been suggested as a potential HBOC risk gene, although its prevalence and penetrance are variable according to populations and type of tumor. We aimed to investigate the prevalence of BARD1 truncating variants in a cohort of patients with clinical suspicion of HBOC. A comprehensive BARD1 screening by multigene panel analysis was performed in 4015 unrelated patients according to our regional guidelines for genetic testing in hereditary cancer. In addition, 51,202 Genome Aggregation Database (gnomAD) non-Finnish, non-cancer European individuals were used as a control population. In our patient cohort, we identified 19 patients with heterozygous BARD1 truncating variants (0.47%), whereas the frequency observed in the gnomAD controls was 0.12%. We found a statistically significant association of truncating BARD1 variants with overall risk (odds ratio (OR) = 3.78; CI = 2.10–6.48; p = 1.16 × 10−5). This association remained significant in the hereditary breast cancer (HBC) group (OR = 4.18; CI = 2.10–7.70; p = 5.45 × 10−5). Furthermore, deleterious BARD1 variants were enriched among triple-negative BC patients (OR = 5.40; CI = 1.77–18.15; p = 0.001) compared to other BC subtypes. Our results support the role of BARD1 as a moderate penetrance BC predisposing gene and highlight a stronger association with triple-negative tumors.

scholarly journals Genetic Variants in the 3’UTR of BRCA1 and BRCA2 Genes and Their Putative Effects on the microRNA Mechanism in Hereditary Breast and Ovarian Cancer

Diagnostics ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 298 ◽  
Author(s):  
María Marisela Sánchez-Chaparro ◽  
Idalia Garza-Veloz ◽  
Omar Alejandro Zayas-Villanueva ◽  
Margarita L. Martinez-Fierro ◽  
Iván Delgado-Enciso ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Genetic Variants ◽  
Binding Sites ◽  
Odds Ratio ◽  
Breast And Ovarian Cancer ◽  
Brca1 And Brca2 ◽  
New Variant ◽  
Brca1 And Brca2 Genes ◽  
Study Population ◽  
New Evidence

Hereditary breast and ovarian cancer (HBOC) syndrome is mainly caused by mutations in the BRCA1 and BRCA2 genes. The 3’UTR region allows for the binding of microRNAs, which are involved in genetic tune regulation. We aimed to identify allelic variants on 3’UTR miRNA-binding sites in the BRCA1 and BRCA2 genes in HBOC patients. Blood samples were obtained from 50 patients with HBOC and from 50 controls. The 3’UTR regions of BRCA1 and BRCA2 were amplified by PCR and sequenced to identify genetic variants using bioinformatics tools. We detected nine polymorphisms in 3’UTR, namely: four in BRCA1 (rs3092995 (C/G), rs8176318 (C/T), rs111791349 (G/A), and rs12516 (C/T)) and five in BRCA2 (rs15869 (A/C), rs7334543 (A/G), rs1157836 (A/G), and rs75353978 (TT/del TT)). A new variant in position c.*457 (A/C) on 3’UTR of BRCA2 was also identified. The following three variants increased the risk of HBOC in the study population: rs111791349-A, rs15869-C, and c.*457-C (odds ratio (OR) range 3.7–15.4; p < 0.05). Genetic variants into the 3’UTR of BRCA1 and BRCA2 increased the risk of HBOC between 3.7–15.4 times in the study population. The presence/absence of these polymorphisms may influence the loss/creation of miRNA binding sites, such as hsa-miR-1248 in BRCA1 3′UTR or the hsa-miR-548 family binding site in BRCA2. Our results add new evidence of miRNA participation in the pathogenesis of HBOC.

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