NGS mutation Profiling of TP53 gene analysis in Oral Squamous Cell Carcinoma (OSCC)

Résumé fourni par la source

The most prevalent cancer in the oral cavity, oral squamous cell carcinoma (OSCC), is a significant public health concern, particularly for Asian populations. One of the main causes of the onset and progression of this illness is mutations in tumor suppressor genes. With mutation rates reported in 60–80% of cases, the TP53 gene is the most frequently mutated gene in OSCC. This study aimed to explore the mutational profile of the TP53 gene in OSCC using next-generation sequencing (NGS) and to evaluate the functional impact of the identified mutations with structural bioinformatics tools. The TP53 protein structure was modelled using the crystal data (PDB ID: 1TSR) from the Protein Data Bank. Mutation data were examined with multiple computational resources, including MMDB for structural annotation, InterProScan and PROSITE for identifying domains and motifs, Protein enrichment analysis for protein-protein interactions, and PDBsum and LigPlot for visualising ligand-binding sites and residue interactions. Additionally, B-factor analysis was conducted to evaluate the structural flexibility and stability of residues within TP53. NGS data showed that most TP53 mutations are located in the DNA-binding domain (DBD), mostly as missense mutations targeting critical residues involved in DNA recognition and transcriptional regulation. Structural insights from MMDB and PDBsum revealed that several mutated residues are located in highly conserved regions crucial for DNA binding and protein stability. B-factor analysis indicated increased flexibility at these mutated sites, which may destabilize the protein's structure. Additionally, protein interaction analysis identified TP53 as interacting with various regulatory proteins that control apoptosis, DNA repair, and the cell cycle. These findings emphasize the significance of combining NGS-based mutation profiling with structural bioinformatics tools to better understand the molecular mechanisms driving OSCC development. The research sheds light on how TP53 mutations compromise structural stability and regulatory interactions, which can lead to tumor formation. Integrating these methods could facilitate the discovery of potential biomarkers and therapeutic targets, advancing precision medicine in oral cancer treatment.

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