Systematic Inspection of the Clinical Relevance of TP53 Missense Mutations in Gastric Cancer

Abstract

The "guardian of the genome," TP53, is one of the most frequently mutated genes of all cancers. Despite the important biological roles of TP53, the clinical relevance of TP53 mutations, in gastric cancer (GC), remains largely unknown. Here, we systematically assessed clinical relevance, in terms of TP53 mutation positions, finding substantial variability. Thus, we hypothesized that the position of the TP53 mutation might affect clinical outcomes in GC. We systematically inspected missense mutations in TP53, from a TCGA (The Cancer Genome Atlas) GC dataset in UCSC Xena repository. Specifically, we examined five aspects of each mutational position: (1) the whole gene body; (2) known hot-spots; (3) the DNA-binding domain; (4) the secondary structure of the domain; and (5) individual mutation positions. We then analyzed the clinical outcomes for each aspect. These results showed that, in terms of secondary structure, patients with mutations in turn regions showed poor prognosis, compared to those with mutations in beta strand regions (log rank ${\text{p}}= {{0.043}}$p=0.043). Also, in terms of individual mutation positions, patients having mutations at R248 showed poorer survival than other patients having mutations at different TP53 positions (log rank ${\text{p}}= {{0.035}}$p=0.035).