<i>BRCA1</i> and <i>BRCA2</i> founder mutations account for 78% of germline carriers among hereditary breast cancer families in Chile

Álvarez, Carolina; Tapia, Teresa; Pérez-Moreno, Elisa; Gajardo-Meneses, Patricia; Ruiz, Catalina; Rios, Mabel; Missarelli, Claudio; Silva, Mariela; Cruz, Antonio Míguez Santa; Matamala, Luis; Carvajal‐Carmona, Luis G.; Camus, Mauricio; Carvallo, Pilar

doi:10.18632/oncotarget.18815

Cited by 42 publications

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“…Several studies from different populations have reported recurrent and founder mutations representing a relevant proportion of BRCA mutation carriers . Brianese et al carried out a BRCA1/2 multiplex ligation‐dependent probe amplification for mutation screening using NGS in which the pathogenic germline mutations of BRCA1 gene (88.2%) were identified .…”

Section: Resultsmentioning

confidence: 99%

“…Variants were identified in the participants and categorized according to variant classification and BRCA1/2 status Pathogenic variants and their distributions in this study BRCA mutation carriers 15. Brianese et al carried out a BRCA1/2 multiplex ligation-dependent probe amplification for mutation screening using NGS in which the pathogenic germline mutations of BRCA1 gene (88.2%) were identified 16.…”

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confidence: 99%

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BRCAmutation characteristics in a series of index cases of breast cancer selected independent of family history

et al. 2019

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Certain genetic predisposition factors, such as BRCA1 and BRCA2 mutations play a pivotal role in familial breast cancer development in both males and females. Due to this, the importance and necessity of genetic screening to identify mutations affecting the population is paramount. Undergoing genetic screenings allows for a more knowledgeable risk assessment for the patients and their care providers. The aim of this study was to evaluate the prevalence of BRCA1/BRCA2 mutated genes in the Turkish population among unselected patients. To identify the molecular markers, we utilized a gene panel analysis consisting of BRCA1 and BRCA2 genes, with a next generation sequencing platform (MiSeq System, Illumina). Sequencing was performed using leukocyte DNA from breast cancer patients. In‐silico analysis for novel mutations was carried out using SIFT, PolyPhen2 and MutationTaster. BRCA1 and BRCA2 pathogenic variants were identified in 18 of 129 (14%) patients among the study population; of those 18 patients, seven (39%) were found in the BRCA1 gene and 11 (61%) in the BRCA2 gene. Ten of the eleven BRCA2 variants (90%) were novel mutations. Four of ten (40%) of the novel mutations were determined to be deleterious and six out of ten (60%) were identified as single nucleotide variations. Clinically significant mutations of the BRCA1/BRCA2 genes are related to an increased susceptibility for breast cancer. There is however, little known about BRCA mutations amongst the general population. Thus, it is important that patients are able to undergo genetic screenings and counseling. This also allows for greater care from health care providers and can only facilitate disease prevention which in turn can lead to a decreased cancer morbidity rate.

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Section: Resultsmentioning

confidence: 99%

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BRCAmutation characteristics in a series of index cases of breast cancer selected independent of family history

et al. 2019

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“…There was also a 9023A>C mutation that causes the BRCA2 protein structure to be replaced by Pro to His. Additionally, nonsense mutations found in Chilean breast cancer families may interfere with normal BRCA2 function [33]. In the Romanian breast cancer, the 4817A>G mutation in exon 11 of the BRCA2 gene was found to change the Lys residue to Arg, which is considered to be a pathogenic mutation [34].…”

Section: Discussionmentioning

confidence: 99%

Case report: Analysis of BRCA1 and BRCA2 gene mutations in a hereditary ovarian cancer family

Liao

Song

et al. 2020

J Assist Reprod Genet

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Objective Breast cancer susceptibility gene 1/2 (BRCA1/2) is the most important susceptibility gene associated with hereditary ovarian cancer (HOC). We aimed to screen BRAC1 and BRAC2 gene mutations in a member of a hereditary ovarian cancer family in China, and to analyze the structure and function of the mutant protein. Methods A typical HOC family was selected. Blood samples and pathological tissue samples were taken from the female members of the family. Blood samples from two patients with sporadic ovaries of the same pathological type were taken as a control group. After RNA extraction, PCR amplification was applied and the PCR products were directly sequenced and aligned, prediction and analysis of protein structure and molecular conformation that may be caused by BRCA1/2 mutation. Results The whole gene analysis of BRCA1 and BRCA2 in ovarian cancer patients in the family showed that there were 8 mutations in BRCA1 whole gene sequencing, including 3 nonsense mutations (2314C>T, 2543T>C, 4540T>C); two mutations have been recorded, which are associated with cervical cancer (2844C>T) and endometriosis (3345A>G); three newly discovered mutations (3780A>G, 5069A>G, 3326A>T). Among them, 3780A>G and 5069A>G caused amino acid changes, while 3326A>T mutation caused Arg mutation to stop codon. A total of 7 mutations were detected in BRCA2 whole-genome sequencing, including 5 non-significant mutations (3623A>G, 4034T>C, 4790A>G, 6740G>C, 7469A>G); one no-record mutation (1716T>A), and 1 recorded mutation (1342A>C), which was associated with breast cancer and ovarian cancer. BRCA1 (3326A>T) and BRCA2 (1342A>C) mutations were co-existing in patients (II1, II3, and II5) identified as serous adenocarcinoma grade II. Two cases of ovarian serous cystadenocarcinoma with no history of family tumors were normalized for BRCA1/2 gene sequencing. In the gene detection of III generation female, four females with BRCA2 (1342A>C) mutation were found, and one of them also carried the BRCA1 (3326A>T) mutation, who can be considered a high-risk group of HOC in this family. Online protein structure predictions revealed that BRCA1 (3326A>T) mutations mutated AGA at this site to TGA resulting in a translated Arg (arginine) mutation as a stop codon, while BRCA2 (1342A>C) mutated AAT at this site to CAT resulting in a translated Asn mutation to His. Conclusion The BRCA1 (3326A>T) and BRCA2 (1342A>C) were detected in the HOC family, which may be the susceptibility gene of the family's HOC. The BRCA1/2 gene screening may be possible to obtain high-risk populations in this family.

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“…BRCA1 and BRCA2 have key roles in the development of breast/ovarian cancer [9,10]. The prevalence of BRCA1/BRCA2 mutations varies in different populations due to founder mutation effect [15,[24][25][26][27][28]. Genetic testing of patients with family history for breast/ovarian cancer have become standard clinical management in Western countries, however, in Tunisia studies of BRCA-associated breast/ovarian cancer remain less investigated.…”

Section: Discussionmentioning

confidence: 99%

Novel and Recurrent BRCA1/BRCA2 Germline Mutations in Patients with Breast /Ovarian Cancer: A Series from the South of Tunisia

Ayed-Guerfali

Kridis-Rejab

Ammous-Boukhris

et al. 2020

Preprint

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Background: The incidence of breast/ovarian cancer is increasing in Tunisia especially in young women and mostly those with family history. However, the spectrum of BRCA mutations remains little explored in Tunisian patients in particular in the southern region. Methods: We sequenced the entire coding regions of BRCA1and BRCA2 genes using Next Generation Sequencing (NGS) in 134 selected patients with breast/ovarian cancer. Results: Among the 134 patients, 19 (14.17%) carried pathogenic mutations (10 are BRCA1 mutation carriers and 9 are BRCA2 mutation carriers) that are mainly frameshisft indel (76.9%). Interestingly, 5 out of the 13 variants (38.46%) were found at least twice in unrelated patients, as the c.1310-1313 delAAGA in BRCA2 and the c.5030_5033 delCTAA that has been identified in 4/98 BC patients and in 3/15 OC patients from unrelated families with strong history of cancer. Besides recurrent mutations, 6 variant (4 in BRCA1 and 2 in BRCA2) were not reported previously. Furthermore, 3 unrelated patients carried the VUS c.9976A>T, (K3326*) in BRCA2 exon 27. BRCA carriers correlated significantly with tumor site (p=0.029) and TNBC cases (p=0.008). In the groups of patients (31-40 y and 41-50 y), BRCA1 mutations occurred more frequently in patients with OC than those with BC, and conversely BRCA2 carriers are mostly affected with BC (p=0.001 and p=0.044 respectively).Conclusions: The overall frequency of the BRCA germline mutations was 14.17% in patients with high risk of breast /ovarian cancer. We identified recurrent mutations as the c.1310_1313 delAAGA in BRCA2 gene and the c.5030_5033 delCTAA in BRCA1 gene that were found in 4% and 20% of familial BC and OC respectively. Our data will contribute in the implementation of genetic counseling and testing for families with high-risk of breast/ovarian cancer.

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BRCA1 and BRCA2 founder mutations account for 78% of germline carriers among hereditary breast cancer families in Chile

Cited by 42 publications

References 44 publications

BRCAmutation characteristics in a series of index cases of breast cancer selected independent of family history

BRCAmutation characteristics in a series of index cases of breast cancer selected independent of family history

Case report: Analysis of BRCA1 and BRCA2 gene mutations in a hereditary ovarian cancer family

Novel and Recurrent BRCA1/BRCA2 Germline Mutations in Patients with Breast /Ovarian Cancer: A Series from the South of Tunisia

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