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ORIGINAL RESEARCH ARTICLE

Examining BRCA1 and BRCA2 Mutations in Gastric Cancer Using Next Generation Sequencing: Relevance for Diagnosis and Treatment Strategies

Hamid Yaz1 Akbar Ali2* Rida Akhtar2
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1 Department of Botany and Microbiology, College of Science, King Saud University Riyadh, P.O. 2455, Riyadh 11451, Saudi Arabia
2 Nishtar Medical University, Multan, Pakistan
CP 2023, 5(3), 2586
Submitted: 12 June 2023 | Accepted: 21 August 2023 | Published: 29 August 2023
© 2023 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

Gastric cancer (GC) presents a significant global health dilemma, being the fifth most widespread cancer on a global scale and the third major contributor to cancer-related deaths. Given the intricacies of this malignancy, there is an urgent need for a thorough investigation into its molecular basis. In this study, we investigated the role of BRCA1 and BRCA2 mutations in Pakistani GC patients and their functional implications. Using Next-Generation Sequencing (NGS), we analyzed BRCA1/2 genes in a cohort of 31 Pakistani GC patients, revealing pathogenic mutations not previously documented in this context. Expression analyses of BRCA1 and BRCA2 genes at both mRNA and protein levels uncovered a consistent down-regulation in GC samples with pathogenic mutations. This down-regulation extends beyond the canonical role of BRCA1/2 in DNA repair, suggesting a broader impact on cellular processes. The clinical significance of these findings lies in the potential of these pathogenic mutations as biomarkers for GC diagnosis and treatment. Furthermore, our study explored potential drugs from the DrugBank database capable of up-regulating BRCA1/2 gene expression in GC treatment. Pathway analysis revealed the involvement of BRCA1/2 genes in diverse pathways, emphasizing their relevance in GC progression. Despite limitations, including a relatively small sample size, this study sheds light on the molecular intricacies of GC and offers promising avenues for further research and personalized therapeutic approaches. In conclusion, our study unveils the presence of pathogenic BRCA1 and BRCA2 mutations in Pakistani GC patients, shedding light on their potential as biomarkers and therapeutic targets. These findings offer promise for enhancing the management and treatment outcomes of this malignancy.

Keywords
Gastric cancer; BRCA1; BRCA2; Mutations; Next Generation Sequencing
Funding
This study did not receive any funding in any form.
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Conflict of interest
The authors declare that they have no conflicts of interest.
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Cancer Plus, Electronic ISSN: 2661-3840 Print ISSN: 2661-3832, Published by AccScience Publishing