Identification of BRCA1 and BRCA2 Germline Mutations in Female Breast Cancer Patients Using Next Generation Sequencing.

BACKGROUND Breast cancer is the most common cancer affecting females according to WHO 2020 report, with BRCA1 and BRCA2 identified as the major tumor suppressor genes linked to disease susceptibility. Hence, the purpose of the current study was to investigate germline mutations among these genes in a group of Egyptian female breast cancer patients. METHODS Blood samples from primary breast cancer patients (n=22), benign breast lesions (n=5) and healthy controls (n=7) were sequenced for BRCA genes by next generation sequencer. RESULTS A total of 135 genetic variations were detected, 59 in BRCA1 and 76 BRCA2, 2 indels (insertion-deletion) and 133 SNV (single nucleotide variation), nearly 55% of those variants were missense variants, 38% were synonymous and 7% were nonsense. A total of 59 variations were detected in BRCA1 and they were categorized as exonic (n=10) and intronic (n=49) regions, BRCA1 exonic variants were categorized into: missense (n=12), non-coding transcript (n=11) synonymous (n=6), splice region synonymous (n=2), stop gain (n=2) and 3-prime UTR (n=1) variants. Regarding variations detected in BRCA2, 55 intronic and 21 exonic variants were identified. Among these 21 variants; 13 novel mutations and 8 formally reported as follows: 7 as benign and one previously reported with contradictory pathogenicity according to the Clinvar database which is a freely available, public archive of reports of the relationships between human variations and phenotypes hosted by the National Center for Biotechnology Information (NCBI) and funded by intramural National Institutes of Health (NIH) funding. CONCLUSION BRCA1 and BRCA2 germline profiling based on next-generation sequencing technology among Egyptian breast cancer female patients revealed 135 germline variations -104 intronic and 31 exonic, respectively. Among the exonic variants; 13 were newly reported mutations. Hence further study is required to enhance mutational analysis which may benefit clinical system.

• Publication year

  2026

• Venue

  Asian Pacific Journal of Cancer Prevention

• Publication date

  2026-02-01

• Fields of study

  Medicine

• Identifiers
  DOI 10.31557/APJCP.2026.27.2.575PMID 41660915
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

• Genetic testing for BRCA1/2 variants in Northern African women with ovarian and breast cancers: a multicentre study of an under-represented ancestry

  2025influential reference
• The Landscape of BRCA Mutations among Egyptian Women with Breast Cancer

  2023cited by this paper
• Prevalence of specific and recurrent/founder pathogenic variants in BRCA genes in breast and ovarian cancer in North Africa

  2021cited by this paper
• Prognostic Impact of BRCA1 and BRCA2 Mutations on Long-Term Survival Outcomes in Egyptian Female Breast Cancer Patients

  2021cited by this paper
• Implications of targeted next-generation sequencing for bladder cancer: report of four cases

  2021cited by this paper
• Impact of circulating miRNA-373 on breast cancer diagnosis through targeting VEGF and cyclin D1 genes

  2021cited by this paper
• Clinical impact of LncRNA XIST and LncRNA NEAT1 for diagnosis of high-risk group breast cancer patients.

  2021influential reference
• Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.

  2021cited by this paper
• BRCA1 and BRCA2 Truncating Mutations and Variants of Unknown Significance in Egyptian Female Breast Cancer Patients.

  2020cited by this paper
• The intronic BRCA1 c.5407-25T>A variant causing partly skipping of exon 23—a likely pathogenic variant with reduced penetrance?

  2020cited by this paper
• Next generation sequencing of BRCA genes in glioblastoma multiform Egyptian patients: a pilot study

  2020cited by this paper
• Twenty Years of BRCA1 and BRCA2 Molecular Analysis at MMCI - Current Developments for the Classification of Variants.

  2019cited by this paper
• Characterization of BRCA1 and BRCA2 genetic variants in a cohort of Bahraini breast cancer patients using next‐generation sequencing

  2019cited by this paper
• BRCA1 and BRCA2 5′ noncoding region variants identified in breast cancer patients alter promoter activity and protein binding

  2018cited by this paper
• A Phase II Study of Talazoparib after Platinum or Cytotoxic Nonplatinum Regimens in Patients with Advanced Breast Cancer and Germline BRCA1/2 Mutations (ABRAZO)

  2018cited by this paper
• Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation

  2018cited by this paper
• PARP inhibitors in breast cancer: Bringing synthetic lethality to the bedside

  2018cited by this paper
• Screening of BRCA1/2 deep intronic regions by targeted gene sequencing identifies the first germline BRCA1 variant causing pseudoexon activation in a patient with breast/ovarian cancer

  2018cited by this paper
• Unique Features of Germline Variation in Five Egyptian Familial Breast Cancer Families Revealed by Exome Sequencing

  2017cited by this paper
• Next-generation sequencing in familial breast cancer patients from Lebanon

  2017cited by this paper
• Identification of novel BRCA founder mutations in Middle Eastern breast cancer patients using capture and Sanger sequencing analysis

  2016cited by this paper
• First application of next-generation sequencing in Moroccan breast/ovarian cancer families and report of a novel frameshift mutation of the BRCA1 gene.

  2016cited by this paper
• The dark matter of the cancer genome: aberrations in regulatory elements, untranslated regions, splice sites, non‐coding RNA and synonymous mutations

  2016cited by this paper
• Contribution of BRCA1 and BRCA2 Germline Mutations to Early Algerian Breast Cancer

  2016cited by this paper
• Updates on breast cancer genetics: Clinical implications of detecting syndromes of inherited increased susceptibility to breast cancer.

  2016cited by this paper
• Mutation spectrum and prevalence of BRCA1 and BRCA2 genes in patients with familial and early‐onset breast/ovarian cancer from Tunisia

  2015cited by this paper
• Gene-panel sequencing and the prediction of breast-cancer risk.

  2015cited by this paper
• Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012

  2015cited by this paper
• Characterization of familial breast cancer in Saudi Arabia

  2015cited by this paper
• Genotype and Phenotype Correlation of Breast Cancer in BRCA MutationCarriers and Non-Carriers

  2015cited by this paper
• Improved understanding of the pathophysiology of atrial fibrillation through the lens of discrete pathological pathways

  2014cited by this paper
• Rapid evolution of BRCA1 and BRCA2 in humans and other primates

  2014cited by this paper
• Screening for common mutations in BRCA1 and BRCA2 genes: interest in genetic testing of Tunisian families with breast and/or ovarian cancer.

  2014cited by this paper
• Two Decades After BRCA: Setting Paradigms in Personalized Cancer Care and Prevention

  2014cited by this paper
• Mutation Screening of the BRCA1 Gene in Early Onset and Familial Breast/Ovarian Cancer in Moroccan Population

  2012cited by this paper
• BRCA1 and BRCA2 germline mutations in Moroccan breast/ovarian cancer families: novel mutations and unclassified variants.

  2012cited by this paper
• Hereditary breast cancer in Middle Eastern and North African (MENA) populations: identification of novel, recurrent and founder BRCA1 mutations in the Tunisian population

  2011cited by this paper
• International network of cancer genome projects

  2010cited by this paper
• BRCA1 and BRCA2 Germline Mutations Screening in Algerian Breast/Ovarian Cancer Families

  2010cited by this paper
• Presymptomatic breast cancer in Egypt: role of BRCA1 and BRCA2 tumor suppressor genes mutations detection

  2010influential reference
• Immunohistochemical detection of estrogen and progesterone receptor and HER2 expression in breast carcinomas: comparison of cell block and tissue block preparations.

  2009cited by this paper
• The Staging of Cancer: A Retrospective and Prospective Appraisal

  2008cited by this paper
• Meta-analysis of BRCA1 and BRCA2 penetrance.

  2007cited by this paper
• Clinical implications of HER‐2/neu overexpression and proteolytic activity imbalance in breast cancer

  2007cited by this paper
• Emerging Role of P53, Bcl‐2 and Telomerase Activity in Egyptian Breast Cancer Patients

  2004influential reference
• Immunohistochemical Evaluation of Hormone Receptor for Routine Practice of Breast Cancer: Highly Sensitive Procedures Significantly Contribute to the Correlation with Biochemical Assays

  2003cited by this paper
• Identification of the breast cancer susceptibility gene BRCA2

  1996cited by this paper
• Histological grading of breast carcinomas: a study of interobserver agreement.

  1995cited by this paper
• Linkage of early-onset familial breast cancer to chromosome 17q21.

  1990cited by this paper

• No citing papers are available for this paper.