TP53 mutation landscape and patient survival in oral squamous cell carcinoma

Abstract Introduction TP53 mutations play a central role in the carcinogenesis of oral squamous cell carcinoma (OSCC). However, due to the diversity of variant patterns of TP53 genetic alterations, the clinical significance of TP53 mutations in OSCC remains poorly understood. Thus, we set out to analyze all exons of the TP53 gene to characterize the TP53 mutation landscape in OSCC and to investigate its associations with clinical outcomes. Methods Treatment-naïve surgical specimens from 124 patients with OSCC were comprehensively analyzed for TP53 mutations using next-generation sequencing. Pathogenicity for each mutation was defined by referring to genomic databases, OncoKB and ClinVar. Multivariable Cox regression analysis was performed to assess the association between the presence of TP53 pathogenic mutations and cancer-specific survival. Results TP53 pathogenic mutations were detected in 81/124 (65%) OSCC cases, comprising 75 different variant patterns. OSCC patients harboring TP53 pathogenic mutations showed shorter cancer-specific survival compared to those without pathogenic mutations (multivariable hazard ratio, 3.70; 95% confidence interval, 1.08–12.61). Moreover, cases with truncating and/or splice mutations showed worse outcomes than other mutation types. Among OSCC patients with stage III/IV, the presence of TP53 pathogenic mutations was significantly associated with shorter survival (P = 0.001), whereas no such association was observed in stage I/II patients (P = 0.89). Conclusions TP53 pathogenic mutations in OSCC have been associated with shorter cancer-specific survival, especially for advanced diseases. Our findings likely attest to the importance of TP53-based molecular classification, leading to the development of novel precision strategies against OSCC.