Clinical validation of an NGS-based assay for the detection of BRCA1 and BRCA2 variants in Chinese patients with breast cancer or ovarian cancer

Objective: Cancer ovary is one of the fatal gynecologic malignancies worldwide. Since breast cancer (BRCA) genes are considered tumor suppressor genes and play important roles in cancer by repairing of chromosomal damage with the error repair of DNA breaks. Therefore, breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) gene mutations strongly enhance the development of ovarian cancer risk among women. Here, we report that both genes are an essential mediator of progress ovarian cancer, to determine the influence of BRCA1 and BRCA2 mutations in the improvement of ovarian cancer.Methods: A total of 25 subjects were chosen for the genetic studies, and three groups were recruited: fifteen ovarian cancer patients group, five healthy controls, and five first-degree relatives to a known case of ovarian cancer patients.Results: A genetic analysis revealed that a strong correlation exists between both gene mutations’ status in ovarian cancer, and BRCA gene mutations (185delAG, 5382insC, and 4153delA in BRCA1 and 6174delT in BRCA2) remained to establish to have a relatively high frequency among people in this study among ovarian cancer patients. Furthermore, seven patients with ovarian cancer carried all of the four investigated mutations, and five had three mutations.Conclusion: Otherwise, BRCA gene frequency showed low prevalence among first-degree relatives, and to a lesser extent among healthy controls, with only a few had all of the mutations combined. These data demonstrate for the first time a molecular link between BRCA1 and BRCA2 mutations in ovarian cancer progression in Iraq.

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Prevalence of BRCA1 and BRCA2 Mutations Among Patients With Ovarian, Primary Peritoneal, and Fallopian Tube Cancer in India: A Multicenter Cross-Sectional Study

JCO Global Oncology ◽

10.1200/go.21.00051 ◽

2021 ◽

pp. 849-861

Author(s):

Sudeep Gupta ◽

Senthil Rajappa ◽

Suresh Advani ◽

Amit Agarwal ◽

Shyam Aggarwal ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Family History ◽

Newly Diagnosed ◽

Brca1 And Brca2 ◽

Brca Mutations ◽

Fallopian Tube Cancer ◽

Cross Sectional ◽

Brca2 Mutations ◽

Brca1 Brca2

PURPOSE There are deficient data on prevalence of germline mutations in breast cancer susceptibility genes 1 and 2 ( BRCA1/ BRCA2) in Indian patients with ovarian cancer who are not selected by clinical features. METHODS This prospective, cross-sectional, noninterventional study in nine Indian centers included patients with newly diagnosed or relapsed epithelial ovarian, primary peritoneal, or fallopian tube cancer. The primary objective was to assess the prevalence of BRCA1/ BRCA2 mutations, and the secondary objective was to correlate BRCA1/ BRCA2 status with clinicopathologic characteristics. Mutation testing was performed by a standard next-generation sequencing assay. RESULTS Between March 2018 and December 2018, 239 patients with a median age of 53.0 (range, 23.0-86.0 years) years were included, of whom 203 (84.9%) had newly diagnosed disease, 36 (15.1%) had family history of ovarian or breast cancer, and 159 (66.5%) had serous subtype of epithelial ovarian cancer. Germline pathogenic or likely pathogenic mutations in BRCA1 and BRCA2 were detected in 37 (15.5%; 95% CI, 11.1 to 20.7) and 14 (5.9%; 95% CI, 3.2 to 9.6) patients, respectively, whereas variants of uncertain significance in these genes were seen in four (1.7%; 95% CI, 0.5 to 4.2) and six (2.5%; 95% CI, 0.9 to 5.4) patients, respectively. The prevalence of pathogenic or likely pathogenic BRCA mutations in patients with serous versus nonserous tumors, with versus without relevant family history, and ≤ 50 years versus > 50 years, were 40 of 159 (25.2%; 95% CI, 18.6 to 32.6) versus 11 of 80 (13.8%; 95% CI, 7.1 to 23.3; P = .0636), 20 of 36 (55.6%; 95% CI, 38.1 to 72.1) versus 41 of 203 (20.2%; 95% CI, 14.9 to 26.4; P < .0001), and 20 of 90 (22.2%; 95% CI, 14.1 to 32.2) versus 31 of 149 (20.8%; 95% CI, 14.6 to 28.2; P = .7956), respectively. CONCLUSION There is a high prevalence of pathogenic or likely pathogenic germline BRCA mutations in Indian patients with ovarian cancer.

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Clinical Implications of the Breast Cancer Susceptibility Genes BRCA1 and BRCA2

Women s Health ◽

10.1517/17455057.1.1.027 ◽

2005 ◽

Vol 1 (1) ◽

pp. 27-34

Author(s):

Steven A Narod

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Cancer Susceptibility ◽

Cancer Chemoprevention ◽

Breast Cancer Susceptibility ◽

High Risk Population ◽

Clinical Genetics ◽

Breast And Ovarian Cancer ◽

Brca1 And Brca2 ◽

Cancer Susceptibility Genes

Genetic testing for BRCA1 and BRCA2 mutations has become an important part of the practice of medical oncology and clinical genetics over the past decade. Increasing numbers of women are requesting a genetic test so that they may better understand their personal risks of breast and ovarian cancer, and so that they may take appropriate measures to reduce the risk. Several of the risk factors can be modified, including breastfeeding and the use of oral contraceptives. A significant number of women opt for preventive mastectomy or oophorectomy, which will dramatically reduce the risks of breast and ovarian cancer. Chemoprevention with tamoxifen is still uncommon, largely due to women's fears of the side effects of the drug. A number of studies have shown that magnetic resonance imaging is superior to conventional mammography in terms of the early detection of breast cancer in the high-risk population. This article explores what is known about assessing genetic risk and the evidence supporting a range of preventive strategies.

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Immunohistochemistry for the detection of BRCA1 and BRCA2 proteins in patients with ovarian cancer: a systematic review

Journal of Clinical Pathology ◽

10.1136/jclinpath-2019-206276 ◽

2019 ◽

Vol 73 (4) ◽

pp. 191-196 ◽

Cited By ~ 3

Author(s):

Lorena Alves Teixeira ◽

Francisco Jose Candido dos Reis

Keyword(s):

Breast Cancer ◽

Systematic Review ◽

Ovarian Cancer ◽

Cancer Type ◽

Loss Of Function ◽

Brca1 And Brca2 ◽

Brca1 Protein ◽

Current Usage ◽

Breast Cancer Type

BackgroundLoss of function in either breast cancer type 1 susceptibility protein (BRCA1) or breast cancer type 2 susceptibility protein (BRCA2) is a major risk factor for epithelial ovarian cancer (EOC) development. BRCA1 or BRCA2 deficiencies are associated with short-term prognosis and might have importance for the treatment of women with the disease. However, the screening of all possible mechanisms of dysfunction is expensive, time-consuming and difficult to apply in clinical practice. On the other hand, immunohistochemistry (IHC) is a simple and reliable method to access the expression of several proteins in tumour tissues.Materials and methodsThis systematic review aims to evaluate the current usage of IHC to detect BRCA1 and BRCA2 deficiencies in EOC. We searched and evaluated all primary literature on the use of IHC for evaluating BRCA1 and BRCA2 proteins expression in EOC. The main concepts for the search were: ovarian neoplasms, IHC, BRCA1 and BRCA2.ResultsForty-four studies from 925 unique titles were included. A total of 4206 tumour samples were evaluated for BRCA1 and 1041 for BRCA2 expression. Twelve BRCA1 primary antibodies were used in 41 studies, and the most common was the MS110 clone (75.6%). Seven BRCA2 primary antibodies were used in ten studies. Using the cut-off of 10%, 47.0% of EOCs are associated with loss of BRCA1 and 34.5% with the loss of BRCA2 expression.ConclusionIHC was effective to detect loss of BRCA1 protein expression in EOC; however, data on BRCA2 expression were heterogeneous and difficult to interpret.

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The Risk of Ovarian Cancer After Breast Cancer in BRCA1 and BRCA2 Carriers

Obstetrical & Gynecological Survey ◽

10.1097/01.ogx.0000157167.69728.df ◽

2005 ◽

Vol 60 (4) ◽

pp. 235-236 ◽

Cited By ~ 6

Author(s):

Kelly A. Metcalfe ◽

Henry T. Lynch ◽

Pariz Ghadirian ◽

Nadine Tung ◽

Ivo A. Olivotto ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Brca1 And Brca2

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Outcome of ovarian cancer after breast cancer in BRCA1 and BRCA2 mutation carriers

British Journal of Cancer ◽

10.1038/bjc.2016.333 ◽

2016 ◽

Vol 115 (10) ◽

pp. 1174-1178 ◽

Cited By ~ 2

Author(s):

Leendert H Zaaijer ◽

Helena C van Doorn ◽

Marian J E Mourits ◽

Marc van Beurden ◽

Joanne A de Hullu ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Brca2 Mutation ◽

Brca1 And Brca2 ◽

Mutation Carriers

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Breast and ovarian cancer risk reduction options for women with pathogenic variables in the brca1 and brca2 genes

Mastology ◽

10.29289/259453942020v30s1050 ◽

2020 ◽

Vol 30 (Suppl 1) ◽

Author(s):

Sandro Vinícius Machado Melo ◽

Thamyse Fernanda de Sa Dassie ◽

Felipe Eduardo Martins de Andrade ◽

Erica Maria Monteiro Santos ◽

Benedito Mauro Rossi

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Risk Reduction ◽

Surgical Management ◽

Tertiary Hospital ◽

Brca1 And Brca2 ◽

Pathogenic Variants ◽

Brca1 And Brca2 Genes ◽

Risk Reduction Measures ◽

Risk Reducing

Introduction: Most breast and ovarian cancers in women are sporadic. However, five to ten percent of these individuals may have an inherited predisposition to cancer (Famorca-Tram, 2015). Women with pathogenic variants in BRCA1 are at risk of breast cancer of up to 72% and of ovarian cancer of up to 44%. Pathogenic variants of the BRCA2 gene increase the risk of breast cancer by up to 69% and of ovarian cancer by up to 25%. Risk reduction measures include: risk-reducing mastectomy, salpingo-oophorectomy, and chemoprevention. For women who do not choose any of these measures, follow-up with periodic examinations is necessary. In this work, the risk reduction measures adopted by 52 women with pathogenic variants in BRCA1 or BRCA2 in a tertiary hospital in São Paulo, Brazil, are analyzed. In addition, it was analyzed what factors could influence the risk-reducing measure adopted. Materials and methods: cross-sectional study with a sample of 52 women with pathogenic variants identified in the BRCA1 and BRCA2 genes seen at a tertiary hospital. Results: 80.8% opted for surgical management as a risk-reducing measure, with 46.2% of women having had prophylactic mastectomy, 11.5% having had bilateral salpingo-oophorectomy, and 23.1% having undergone both surgical procedures. Non-surgical management occurred in 19.2% of the cases, with 8% (3 cases) undergoing chemoprophylaxis with tamoxifen and 15.4% undergoing surveillance. Conclusion: Most patients opted for surgical intervention, with risk-reducing mastectomy being the most frequent one, followed by salpingo-oophorectomy. When testing was not requested by the geneticist, there was a greater tendency toward the surgical option.

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Comprehensive profiling of BRCA1 and BRCA2 variants in breast and ovarian cancer in Chinese patients

Human Mutation ◽

10.1002/humu.23965 ◽

2019 ◽

Vol 41 (3) ◽

pp. 696-708 ◽

Cited By ~ 4

Author(s):

Xianqi Gao ◽

Xiyan Nan ◽

Yilan Liu ◽

Rui Liu ◽

Wanchun Zang ◽

...

Keyword(s):

Ovarian Cancer ◽

Chinese Patients ◽

Breast And Ovarian Cancer ◽

Brca1 And Brca2

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Frequency and spectrum of founder and non-founder BRCA1 and BRCA2 mutations in a large series of Russian breast cancer and ovarian cancer patients

Breast Cancer Research and Treatment ◽

10.1007/s10549-020-05827-8 ◽

2020 ◽

Vol 184 (1) ◽

pp. 229-235

Author(s):

Anna P. Sokolenko ◽

Tatiana N. Sokolova ◽

Valeria I. Ni ◽

Elena V. Preobrazhenskaya ◽

Aglaya G. Iyevleva ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Cancer Patients ◽

Large Series ◽

Brca1 And Brca2 ◽

Brca2 Mutations ◽

Brca1 And Brca2 Mutations

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

Colombia Medica ◽

10.25100/cm.v50i3.2385 ◽

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.

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