TP53 Exon 8 Mutations are Associated with Shorter Survival in Advanced Lung Cancer Patients

Abstract

Background: Currently, in clinical settings, all TP53 mutations have been considered equally. However, increasing evidence has triggered us to challenge such practice. Numerous studies with conflicting results have revealed the position and type of mutation have differential effects on prognosis. Such disparity can be partially attributed to the lack of unifying classification system for TP53 mutations. In this study, we compared 2 most frequently used systems, according to location or its functional effects on p53 protein, and analyzed the impact of TP53 mutations on survival in 379 advanced Chinese lung cancer patients. Methods: We performed capture-based ultra-deep targeted sequencing on plasma samples of 379 Chinese advanced lung patients. Findings: Our results show that mutations occurring in exon 8 are correlated with shorter overall survival (OS) in tyrosine kinase inhibitor (TKI)-naive (p=0.013) and previously treated with 1 line of TKI patients (p=0.032). Such mutations showed a trend of correlating with shorter OS in patients treated with 2 lines of previous treatment. The correlation between OS and TP53 mutation categorized by function or considered collectively, was not consistent across diverse treatment history. Interpretation: Our results provide solid evidence that not all TP53 mutations are equal. Exon 8 mutations can identify a subgroup of patients with unfavorable prognosis across diverse treatment history. It is the first study which compared and contrasted different TP53 mutation classification systems in a large cohort of advanced lung cancer patients. Funding Statement: This work was supported by the National Nature Science Foundation of China (81672284), and a foundation of Third Military Medical University (2012XLC08). The funders of the study have no role in study design, data analysis, data interpretation or writing of the report. Declaration of Interests: The authors declare no conflicts of interests. Ethics Approval Statement: This study was approved by the ethic committee at Chongqing Daping Hospital.