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Original Research

Open Access

Next generation sequencing analysis of BRCA1/2 genes reveals clinically significant pathogenic mutations in ovarian cancer patients

  • Yang Gao1
  • Shengqi Su1
  • Rida Naz2,*,
  • Xufei Yao1,*,

1Lishui Hospital of traditional Chinese medicine, 317312 Lishui, Zhejiang, China

2Regional Blood Centre, KPK Health Program, 29111 Dera Ismail Khan, Pakistan

DOI: 10.22514/ejgo.2024.051 Vol.45,Issue 3,June 2024 pp.75-87

Submitted: 23 August 2023 Accepted: 22 September 2023

Published: 15 June 2024

*Corresponding Author(s): Rida Naz E-mail:
*Corresponding Author(s): Xufei Yao E-mail:


Ovarian cancer is a formidable global health concern, necessitating extensive research to unravel its underlying genetic and epigenetic complexities. This study focuses on dissecting the role of Breast Cancer Gene 1 (BRCA1) and Breast Cancer Gene 2 (BRCA2) genes within the context of ovarian cancer in the Pakistani population. Employing Next-Generation Sequencing (NGS), we conducted a comprehensive mutational analysis of BRCA1/2 somatic mutations. Kaplan Meier analysis was used to analyze the effect of pathogenic mutations on the survival outcomes of the ovarian cancer patients. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Immunohistochemistry (IHC) analyses were conducted to analyze the down-stream effect of the pathogenic mutations. Targeted bisulfite sequencing (bisulfite-seq) analysis facilitated the investigation of epigenetic contribution to gene expression regulation. Enrichment analysis was conducted to uncover significant Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with BRCA1/2. Exploring DrugBank, we identified potential drugs capable of modulating BRCA1/2 expression regulation. NGS analysis identified four clinically significant pathogenic mutations within the BRCA1 gene and two within the BRCA2 gene, shedding light on their potential involvement in ovarian cancer susceptibility and progression. Kaplan Meier analysis unveiled poor overall survival (OS) associated with the identified pathogenic mutations, accentuating their prognostic value. Expression analysis using RT-qPCR and IHC demonstrated a significant up-regulation of BRCA1 and BRCA2 genes in ovarian cancer samples harboring pathogenic mutations. Bisulfite-seq revealed a significant hypomethylation within promoter regions of mutated BRCA1 and BRCA2 genes in ovarian cancer samples, compared to non-mutated cases with pathogenic mutations, indicating the role of epigenetics in in expression dysregulation as well. We unveil clinically important pathogenic mutations and demonstrate their association with altered gene expression. These findings collectively contribute to a deeper comprehension of ovarian cancer etiology, potentially paving the way for personalized therapeutic interventions.


Ovarian cancer; BRCA1; BRCA2; Mutation

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Yang Gao,Shengqi Su,Rida Naz,Xufei Yao. Next generation sequencing analysis of BRCA1/2 genes reveals clinically significant pathogenic mutations in ovarian cancer patients. European Journal of Gynaecological Oncology. 2024. 45(3);75-87.


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