Mutations in exon 8 of TP53 are associated with shorter survival in patients with advanced lung cancer.

ABSTRACT

Currently, in clinical settings, all TP53 mutations have been considered equally. However, numerous studies have demonstrated that the position and type of mutation have differential effects on prognosis. Such discrepancy can be partially due to the lack of unifying classification system for TP53 mutations. In the present study, two of the most frequently used systems were compared, according to the location of the mutation or its functional effects on p53 protein and the impact of TP53 mutations on the overall survival (OS) time of 379 Chinese patients with advanced lung cancer was analyzed. Capture-based ultra-deep targeted sequencing on plasma samples of 379 patients with advanced lung cancer was performed. The present results suggested that mutations occurring in exon 8 may be associated with shorter OS in tyrosine kinase inhibitor-naïve patients (P=0.013) and in patients previously treated with one line of treatment (P=0.032). The results of the present study provided solid evidence that not all TP53 mutations were associated with a similar prognosis. Mutations in exon 8 were found in a subgroup of patients with unfavorable prognosis across various treatment histories. To the best of our knowledge, the present study is the first to compare different TP53 mutation classification systems in a large cohort of patients with advanced lung cancer.