scholarly journals BRCA1 novel mutation V1736D and in silico analysis of SNP Q356R in Sudanese patients with breast cancer

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1461
Author(s):  
Mohamed Elmogtba Mouaweia Mohamed Aabdein ◽  
Alsmawal Awad Mohammed Elimam ◽  
Hisham N. Altayb ◽  
Mohamed El-Fatih Mohy Eldeen ◽  
Mosab Mohamed Gasemelseed ◽  
...  
Keyword(s):  
Breast Cancer ◽  
In Silico ◽  
Novel Mutation ◽  
Disease Onset ◽  
Missense Mutations ◽  
Nucleotide Polymorphisms ◽  
Protein Activity ◽  
Exon 11 ◽  
Exon 20 ◽  
Novel Snp

Background: Breast cancer (BC) remains one of the leading causes of death in women worldwide. The BRCA1 deleterious mutation has a significant role in developing BC, and the risk has been estimated to be 46–87%. Many studies emphasize the need for mining BRCA1 gene mutations that might have a role in BC pathogenesis and could affect early disease onset. This study was conducted to screen for possible pathogenic single nucleotide polymorphisms (SNPs) in BRCA1, targeting three regions: two in exon 11 and the third in exon 20. Methods: 45 blood samples were collected from patients diagnosed with BC. DNA was extracted and selected regions were amplified by PCR using three sets of primers - two within exon 11 and one within exon 20 of BRCA1. Subsets of 10 samples were selected for each primer set (30 PCR products) and sequenced. Sequences were analyzed using various bioinformatics tools. Results: Two missense mutations were found, Q356R (rs1799950) in one patient (27 years old) and a novel SNP, V1736D, in three premenopausal patients (≤45 years), which were located within exons 11 and 20, respectively. Both detected variants were heterozygous, a status found in all patients detected with such monoallelic variation. Both missense variants underwent in silico analysis. The well-known mutation, rs1799950, was predicted to alter the protein activity, conferred by a mutant residue (R-Arg), owing to the position with a bigger size and positive charge. The novel SNP, V1736D, was predicted to play a role in the pathogenesis of BC. Conclusion: Both variants require further investigation, firstly to assess their contribution to BC and secondly to determine their potential diagnostic value when assessed in a larger population.

scholarly journals BRCA1 novel mutation V1736D and in silico analysis of SNP Q356R in Sudanese patients with breast cancer

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1461
Author(s):  
Mohamed Elmogtba Mouaweia Mohamed Aabdein ◽  
Alsmawal Awad Mohammed Elimam ◽  
Hisham N. Altayb ◽  
Mohamed El-Fatih Mohy Eldeen ◽  
Mosab Mohamed Gasemelseed ◽  
...  
Keyword(s):  
Breast Cancer ◽  
In Silico ◽  
Novel Mutation ◽  
Disease Onset ◽  
Missense Mutations ◽  
Nucleotide Polymorphisms ◽  
Protein Activity ◽  
Exon 11 ◽  
Exon 20 ◽  
Novel Snp

Background: Breast cancer (BC) remains one of the leading causes of death in women worldwide. The BRCA1 deleterious mutation has a significant role in developing BC, and the risk has been estimated to be 46–87%. Many studies emphasize the need for mining BRCA1 gene mutations that might have a role in BC pathogenesis and could affect early disease onset. This study was conducted to screen for possible pathogenic single nucleotide polymorphisms (SNPs) in BRCA1, targeting three regions: two in exon 11 and the third in exon 20. Methods: 45 blood samples were collected from patients diagnosed with BC. DNA was extracted and selected regions were amplified by PCR using three sets of primers - two within exon 11 and one within exon 20 of BRCA1. Subsets of 10 samples were selected for each primer set (30 PCR products) and sequenced. Sequences were analyzed using various bioinformatics tools. Results: Two missense mutations were found, Q356R (rs1799950) in one patient (27 years old) and a novel SNP, V1736D, in three premenopausal patients (≤45 years), which were located within exons 11 and 20, respectively. Both detected variants were heterozygous, a status found in all patients detected with such monoallelic variation. Both missense variants underwent in silico analysis. The well-known mutation, rs1799950, was predicted to alter the protein activity, conferred by a mutant residue (R-Arg), owing to the position with a bigger size and positive charge. The novel SNP, V1736D, was predicted to play a role in the pathogenesis of BC. Conclusion: Both variants require further investigation, firstly to assess their contribution to BC and secondly to determine their potential diagnostic value when assessed in a larger population.

scholarly journals BRCA1 novel mutation V1736D and in silico analysis of SNP Q356R in Sudanese patients with breast cancer

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1461
Author(s):  
Mohamed Elmogtba Mouaweia Mohamed Aabdein ◽  
Alsmawal Awad Mohammed Elimam ◽  
Hisham N. Altayb ◽  
Mohamed El-Fatih Mohy Eldeen ◽  
Mosab Mohamed Gasemelseed ◽  
...  
Keyword(s):  
Breast Cancer ◽  
In Silico ◽  
Novel Mutation ◽  
Disease Onset ◽  
Missense Mutations ◽  
Nucleotide Polymorphisms ◽  
Protein Activity ◽  
Exon 11 ◽  
Exon 20 ◽  
Novel Snp

Background: Breast cancer (BC) remains one of the leading causes of death in women worldwide. The BRCA1 deleterious mutation has a significant role in developing BC, and the risk has been estimated to be 46–87%. Many studies emphasize the need for mining BRCA1 gene mutations that might have a role in BC pathogenesis and could affect early disease onset. This study was conducted to screen for possible pathogenic single nucleotide polymorphisms (SNPs) in BRCA1, targeting three regions: two in exon 11 and the third in exon 20. Methods: 45 blood samples were collected from patients diagnosed with BC. DNA was extracted and selected regions were amplified by PCR using three sets of primers - two within exon 11 and one within exon 20 of BRCA1. Subsets of 10 samples were selected for each primer set (30 PCR products) and sequenced. Sequences were analyzed using various bioinformatics tools. Results: Two missense mutations were found, Q356R (rs1799950) in one patient (27 years old) and a novel SNP, V1736D, in three premenopausal patients (≤45 years), which were located within exons 11 and 20, respectively. Both detected variants were heterozygous, a status found in all patients detected with such monoallelic variation. Both missense variants underwent in silico analysis. The well-known mutation, rs1799950, was predicted to alter the protein activity, conferred by a mutant residue (R-Arg), owing to the position with a bigger size and positive charge. The novel SNP, V1736D, was predicted to play a role in the pathogenesis of BC. Conclusion: Both variants require further investigation, firstly to assess their contribution to BC and secondly to determine their potential diagnostic value when assessed in a larger population.

scholarly journals BRCA1 novel variation V1736D and in silico analysis of SNP Q356R in Sudanese patients with breast cancer

F1000Research ◽  
2018 ◽  
Vol 6 ◽  
pp. 1461
Author(s):  
Mohamed Elmogtba Mouaweia Mohamed Aabdein ◽  
Alsmawal Awad Mohammed Elimam ◽  
Hisham N. Altayb ◽  
Mohamed El-Fatih Mohy Eldeen ◽  
Mosab Mohamed Gasemelseed ◽  
...  
Keyword(s):  
Breast Cancer ◽  
In Silico ◽  
Disease Onset ◽  
In Silico Analysis ◽  
Diagnostic Value ◽  
Nucleotide Polymorphisms ◽  
Protein Activity ◽  
Exon 11 ◽  
Exon 20 ◽  
Novel Snp

Background: Breast cancer (BC) remains one of the leading causes of death in women worldwide. The BRCA1 deleterious mutation has a significant role in developing BC, and the risk has been estimated to be 46–87%. Many studies emphasize the need for mining BRCA1 gene mutations that might have a role in BC pathogenesis and could affect early disease onset. This study was conducted to screen for possible pathogenic single nucleotide polymorphisms (SNPs) in BRCA1, targeting three regions: two in exon 11 and the third in exon 20. Methods: 45 blood samples were collected from patients diagnosed with BC. DNA was extracted and selected regions were amplified by PCR using three sets of primers - two within exon 11 and one within exon 20 of BRCA1. Subsets of 10 samples were selected for each primer set (30 PCR products) and sequenced. Sequences were analyzed using various bioinformatics tools. Results: Two missense variations were found, Q356R (rs1799950) in one patient (27 years old) and a novel SNP, V1736D, in three premenopausal patients (≤45 years), which were located within exons 11 and 20, respectively. Both detected variants were heterozygous, a status found in all patients detected with such monoallelic variation. Both missense variants underwent in silico analysis. The well-known variation, rs1799950, was predicted to alter the protein activity, conferred by a mutant residue (R-Arg), owing to the position with a bigger size and positive charge. The novel SNP, V1736D, was predicted to play a role in the pathogenesis of BC. Conclusion: Both variants require further investigation, firstly to assess their contribution to BC and secondly to determine their potential diagnostic value when assessed in a larger population.

scholarly journals Detection of a novel mutation in exon 20 of the BRCA1 gene

2013 ◽  
Vol 18 (4) ◽  
Author(s):  
Abhijit Chakraborty ◽  
Atul Katarkar ◽  
Keya Chaudhuri ◽  
Ashis Mukhopadhyay ◽  
Jayasri Basak
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Hereditary Breast Cancer ◽  
Tumor Suppressor Genes ◽  
Novel Mutation ◽  
Mutation Screening ◽  
Brct Domain ◽  
Globular Domain ◽  
Suppressor Genes ◽  
Exon 20

AbstractHereditary breast cancer constitutes 5–10% of all breast cancer cases. Inherited mutations in the BRCA1 and BRCA2 tumor-suppressor genes account for the majority of hereditary breast cancer cases. The BRCA1 C-terminal region (BRCT) has a functional duplicated globular domain, which helps with DNA damage repair and cell cycle checkpoint protein control. More than 100 distinct BRCA1 missense variants with structural and functional effects have been documented within the BRCT domain. Interpreting the results of mutation screening of tumor-suppressor genes that can have high-risk susceptibility mutations is increasingly important in clinical practice. This study includes a novel mutation, p.His1746 Pro (c.5237A>C), which was found in BRCA1 exon 20 of a breast cancer patient. In silico analysis suggests that this mutation could alter the stability and orientation of the BRCT domain and the differential binding of the BACH1 substrate.

scholarly journals Genetic Variants in the Promoter Region of miR-10b and the Risk of Breast Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Jiaping Chen ◽  
Yue Jiang ◽  
Jing Zhou ◽  
Sijun Liu ◽  
Yayun Gu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Nucleotide Polymorphisms ◽  
In Silico ◽  
Promoter Region ◽  
Cancer Susceptibility ◽  
Chinese Women ◽  
Close Association ◽  
Breast Cancer Susceptibility ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

Variants in microRNA genes may affect their expression by interfering with the microRNA maturation process and may substantially contribute to the risk of breast cancer. Recent studies have identified miR-10b as an interesting candidate because of its close association with the metastatic behavior of breast cancer. However, the roles of miR-10b-related single nucleotide polymorphisms in breast cancer susceptibility remain unclear. This case-control study evaluated the associations between variants in the upstream transcription regulation region of miR-10b and the risk of breast cancer among Chinese women. Seven potentially functional SNPs were investigated using genotyping assays. The potential biological functions of the identified positive SNPs were further evaluated using in silico databases. We found that rs4078756, which was located at the promoter region of miR-10b, was significantly associated with breast cancer risk (rs4078756 AG/GG versus AA, adjusted odds ratio: 1.17, 95% confidence interval: 1.02–1.35). The other six single nucleotide polymorphisms exhibited negative associations. Based on the in silico prediction, rs4078756 potentially regulated miR-10b expression through promoter activation or repression. These findings indicate that a potentially functional SNP (rs4078756) in the promoter region of miR-10b may contribute to breast cancer susceptibility among Chinese women.

scholarly journals BRCA1 and BRCA2 mutations in breast and ovarian cancer families from south west Colombia

2020 ◽  
pp. 163-175
Author(s):  
Laura Cifuentes-C ◽  
Ana Lucia Rivera-Herrera ◽  
Guillermo Barreto
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
In Silico ◽  
Novel Mutation ◽  
In Silico Analysis ◽  
Moderate Increase ◽  
Brca1 And Brca2 ◽  
Variants Of Uncertain Significance ◽  
Uncertain Significance ◽  
Colombian Pacific

Introduction: Breast cancer is the most common neoplasia of women from all over the world especially women from Colombia. 5%­10% of all cases are caused by hereditary factors, 25% of those cases have mutations in the BRCA1/BRCA2 genes. Objective: The purpose of this study was to identify the mutations associated with the risk of familial breast and/or ovarian cancer in a population of Colombian pacific. Methods: 58 high-risk breast and/or ovarian cancer families and 20 controls were screened for germline mutations in BRCA1 and BRCA2, by Single Strand Conformation Polymorphism (SSCP) and sequencing. Results: Four families (6.9%) were found to carry BRCA1 mutations and eight families (13.8%) had mutations in BRCA2. In BRCA1, we found three Variants of Uncertain Significance (VUS), of which we concluded, using in silico tools, that c.81­12C>G and c.3119G>A (p.Ser1040Asn) are probably deleterious, and c.3083G>A (p.Arg1028His) is probably neutral. In BRCA2, we found three variants of uncertain significance: two were previously described and one novel mutation. Using in silico analysis, we concluded that c.865A>G (p.Asn289Asp) and c.6427T>C (p.Ser2143Pro) are probably deleterious and c.125A>G (p.Tyr42Cys) is probably neutral. Only one of them has previously been reported in Colombia. We also identified 13 polymorphisms (4 in BRCA1 and 9 in BRCA2), two of them are associated with a moderate increase in breast cancer risk (BRCA2 c.1114A>C and c.8755­66T>C). Conclusion: According to our results, the Colombian pacific population presents diverse mutational spectrum for BRCA genes that differs from the findings in other regions in the country.

scholarly journals In-silico analysis to identify the role of MEN1 missense mutations in breast cancer

2020 ◽  
Vol 19 (06) ◽  
pp. 2041002
Author(s):  
Satishkumar Ranganathan Ganakammal ◽  
Mahesh Koirala ◽  
Bohua Wu ◽  
Emil Alexov
Keyword(s):  
Breast Cancer ◽  
In Silico ◽  
Multiple Endocrine Neoplasia ◽  
Breast Cancer Tissue ◽  
Cancer Tissue ◽  
Missense Mutations ◽  
Loss Of Function ◽  
Men1 Gene ◽  
Endocrine Neoplasia ◽  
The Impact

Background: The multiple endocrine neoplasia type 1 (MEN1) gene located on chromosome 11q13 encodes menin protein. Previously reported mutations were thought to result in loss of function of menin protein and that they are associated with multiple endocrine neoplasia 1 disorder. However, recently menin has also been characterized as an oncosuppressor protein and it was suggested that mutations in it are associated with various other tumors. Studies indicate that the menin protein stimulates the estrogen receptor (ER) that in turn increases the predisposition for inherited breast cancer. Methods: Here, we used our supervised in-house combinatory in-silico predictor method to investigate the impact of unclassified missense mutations in MEN1 gene found in breast cancer tissue. We also examined the biophysical and biochemical properties to predict the effects of these missense variants on the menin protein stability and interactions. The results are compared with the effects of known pathogenic mutations in menin causing neoplasia. Results: Our analysis indicates that some of the variants found in breast cancer tissue show similar pattern of destabilizing the menin protein and its interactions as the pathogenic variants associated with neoplasia. Taking together with the results of our in-silico consensus predictor, we classify missense mutations in menin protein found in breast cancer tissue into pathogenic and benign, and thus, suggesting as an indicator for early detection of elevated breast cancer risk.

Investigating the impact of missense mutations in hCES1 by in silico structure-based approaches

2016 ◽  
Vol 31 (2) ◽  
Author(s):  
Grace Shema Nzabonimpa ◽  
Henrik Berg Rasmussen ◽  
Søren Brunak ◽  
Olivier Taboureau ◽  
for the INDICES Consortium
Keyword(s):  
Drug Dosage ◽  
Structural Level ◽  
Missense Mutations ◽  
Nucleotide Polymorphisms ◽  
Protein Activity ◽  
Metabolizing Enzymes ◽  
Functional Sites ◽  
Therapeutic Outcomes ◽  
Activity Structure ◽  
The Impact

AbstractGenetic variations in drug-metabolizing enzymes have been reported to influence pharmacokinetics, drug dosage and other aspects that affect therapeutic outcomes. Most particularly, non-synonymous single-nucleotide polymorphisms (nsSNPs) resulting in amino acid changes disrupt potential functional sites responsible for protein activity, structure, or stability, which can account for individual susceptibility to disease and drug response. Investigating the impact of nsSNPs at a protein’s structural level is a key step in understanding the relationship between genetic variants and the resulting phenotypic changes. For this purpose,

scholarly journals Single nucleotide polymorphism rs1799794 in XRCC3 gene on breast cancer patients

2021 ◽  
Vol 62 (2) ◽  
pp. 5-9
Author(s):  
Thi Thu Thao Nguyen ◽  
◽  
Thu Thuy Nguyen ◽  
Vu Viet Ha Vuong ◽  
Huy Thinh Tran ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Onset ◽  
Strand Break ◽  
Control Group ◽  
Case Group ◽  
Protective Effects ◽  
Nucleotide Polymorphisms ◽  
Breast Cancer Patients ◽  
Single Nucleotide ◽  
Xrcc3 Gene

The single nucleotide polymorphisms of the XRCC3 gene including rs1799794 affect the DNA double-strand break/repair. Therefore, it plays a critical part in the initiation of carcinogenesis. This study aimed to investigate the distribution of rs1799794 and the association between rs1799794 and breast cancer risk. The study was performed in 208 Vietnamese females suffering from breast cancer and 208 age-matched normal healthy controls. DNA was extracted from whole blood whilst genotyping was conducted using PCR-RFLP. The results show that the frequency of the A and G allele in the case group are 0.575 and 0.425, in the control group are 0.548 and 0.452. The frequency of AA, AG, GG genotype in the case group are 34.6, 45.7, and 19.7%; in the control group are 33.2, 43.3, and 23.5%. AG genotype of rs1799794 associated with disease onset early of breast cancer, increasing the risk of breast cancer among those who were 45 years old and younger. The GG genotype has protective effects and reduces the risk of breast cancer in the age group ≤45 years.

Evaluation of EZH2 SNPs in cholangiocarcinoma patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10611-10611
Author(s):  
Elisa Paolicchi ◽  
Paola Pacetti ◽  
Elisa Giovannetti ◽  
Andrea Mambrini ◽  
Massimo Orlandi ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
In Silico ◽  
Functional Characterization ◽  
Polycomb Group ◽  
Missense Mutations ◽  
Nucleotide Polymorphisms ◽  
Polycomb Group Protein ◽  
Treatment Optimization ◽  
Logrank Test ◽  
Risk Of Death

10611 Background: Cholangiocarcinoma (CCA) is an aggressive tumor arising from biliary tract epithelium.CCA is the second most common primary hepatic malignancy, with a progressive increasing incidence in western countries. Polycomb group protein Enhancer of Zeste homolog 2 (EZH2) is overexpressed in several human carcinomas, including CCA, where EZH2 overexpression is associated with tumor progression. The aim of this study is to evaluate the correlation between candidate EZH2 Single Nucleotide Polymorphisms (SNPs) with clinical outcome in CCA patients. Methods: Genomic DNA was extracted from blood samples of 75 patients [44 male and 31 female, with average age of 62.3 (range, 26-80 years)] affected by hystologically confirmed advanced CCA, treated with the epirubicin-cisplatin-xeloda (ECX) regimen. We performed an in silico characterization to select EZH2 SNPs (rs2302427 C/G, rs6464926 C/T, rs17171119 T/G and rs887569 C/T) from 26 EZH2 SNPs described previously. Genotyping was performed through Taqman PCR. Prognostic value of selected EZH2 SNPs was assesses by correlation with time to progression (TTP) and overall survival (OS). OS and TTP curves were obtained through Kaplan-Meier method, and comparison with survival distribution was evaluated with logrank test. Results: Through specific software (PROMO 3.0, MicroSNiper and Gene Card) we performed an in silico analysis based on functional characterization criteria (transcription factor binding-TFB, miRNA binding and missense mutations). We selected 4 EZH2 SNP alleles showing specific relevance in CCA because of their differential TFB affinity (PPARα/RXRα, E2F-1, Pax-5 and p53). The rs887569 C/T SNP was significantly associated with clinical outcome. The TT genotype predicted a significantly longer OS in CCA patients (TT vs CT-CC p=0.026). Moreover, the TT genotype showed a trend-like association with reduced risk of death (HR=0.59, 95%CI=0.33-1.05, p=0.075), at multivariate analysis. Conclusions: These results suggest the role of rs887569 EZH2 SNP as a possible predictive marker of OS in advanced CCA patients treated with ECX regimen, and offer a potential new tool for treatment optimization.

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