The Impact of Specific High-Pathogenic Tp53 Mutations on Survival in Head and Neck Cancers

Abstract

Head and neck cancers (HNC) constitute about 30-40 % of all cancers in India. tp53 tumor suppressor gene is the most common gene mutated in HNC but has not been demonstrated to have any diagnostic or prognostic significance. therefore, we hypothesize that the survival rate and prognosis of head and neck cancer patients are linked with certain specific high-pathogenic tp53 hot spot mutations. To evaluate the hypothesis, we conducted a retrospective study on a cohort of 100 HNC patients between April 2013 and April 2018. targeted deep sequencing was performed to identify specific somatic mutations. Kaplan–Meier analysis and log-rank tests were performed. Tp53 mutations were identified in 47 of the 100 cases, with dual mutations in 4 patients. Functional characteristics displayed loss of function in 54.9% and gain of function in 27.5 % of cases. the majority of cases displayed missense aberration (74.5%), followed by nonsense mutations (11.76%). Of these pathogenic mutations, 33.3% fell into 6 hot spot residues while mini hot spot residues constituted 20.5% of the mutations. There was no statistically significant difference in the median survival rate between patients with and without the out tp53 mutation. however, the median survival rate was linked with poor prognosis in patients with specific pathogenic hot spot mutations in 247, 248, 245, and 175 residues (p value= 0.028). The majority of hot spot mutations (66%) showed a gain of function which may have been contributory to the pathogenicity of the disease. Results provide evidence that the existence of high-pathogenicity hot spot residues appears to be the only mutation that warrants further research to identify the therapeutic and prognostic significance of the tp53 gene in the treatment of HNC. further systemic studies are recommended to validate this hypothesis.