Abstract
Head and Neck Squamous Cell Carcinoma (HNSC) presents a formidable challenge in the field of oncology due to its aggressive nature and the limited therapeutic options available. In this study, our primary focus was on the Pakistani HNSC patient population, aiming to investigate germline oncogenic mutations within the BRCA1 and BRCA2 genes via Next Generation Sequencing (NGS) and explore their clinical implications. We sought to understand the functional consequences of these mutations via RT-qPCR and Immunohistochemistry (IHC) techniques. The key discovery of our research lies in the identification of three pathogenic mutations, including two within BRCA1 (p.Cys274Ter and p.Glu272Ter) and one within BRCA2 (p.Met1Val), among Pakistani HNSC patients. These mutations previously associated with an increased risk of various cancers. What sets our study apart is the uniqueness of these pathogenic mutations, absent in HNSC patients from other populations. This suggests a distinct genetic profile in Pakistani HNSC patients, possibly contributing to their susceptibility to this malignancy. Furthermore, our research revealed elevated expression levels of BRCA1 and BRCA2 genes in HNSC samples harboring pathogenic mutations, offering insights into mechanisms driving tumor progression in HNSC. Importantly, we identified significant enrichment of BRCA1/2 genes in pathways related to cancer development within the KEGG database. Finally, in our quest to explore therapeutic avenues, we systematically analyzed drugs targeting up-regulated and mutated BRCA1/2 genes, identifying promising candidates for tailored treatment modalities in HNSC. In conclusion, our study reveals the unique genetic profile of HNSC in Pakistani patients, featuring unique pathogenic mutations in BRCA1 and BRCA2 genes. These mutations offer promise as valuable diagnostic markers and potential therapeutic targets.