TP53 Mutation Mapping in Advanced Non-Small Cell Lung Cancer: A Real-World Retrospective Cohort Study

Abstract

Background: TP53 is frequently mutated in solid tumors, but its basic mutation mapping is mixed, particularly in aggressive-stage lung cancer. Experimental Design: We curated a total of 139 advanced non-small cell lung cancer (NSCLC) patients who harbored wild-type TP53 (TP53wt) or mutated TP53 (TP53mut) based on next-generation sequencing (NGS) to analyze multiple-dimensional data types, including tumor mutation burden (TMB), programmed death receptor ligand 1 (PD-L1) expression, co-mutant alterations, hotspot mutations distribution, and therapy response. Results: TP53 was evident in 125 mutations and significantly associated with male sex, adenocarcinoma differentiation, smoking history, PD-L1 tumor proportion score, and TMB level. The most frequent mutations were distributed on exon 8, but there were no distinct hotspot mutations. After outlining the co-mutation genes, it is interesting to note that DNA damage repair (DDR) genes were frequent alterations in the mutated TP53 cohort. Even though there was no significant difference between the TP53wt and TP53mut cohorts on therapy response, patients with nucleotide variation in G>T achieved a relatively higher durable clinical benefit (DCB) rate. Conclusions: This real-world retrospective study suggests that molecular stratification on the basis of TP53 mutations should be deeply explored for NSCLC to optimize and modify clinical therapy choices.

Keywords

• TP53
• non-small cell lung cancer
• co-mutation status
• therapy response