418P - Mutational landscape of non-small cell lung cancer in the United States

Background

Mutational landscape studies, facilitated by next-generation sequencing technologies, can improve our understanding of cancer pathogenesis and help identify potentially targetable alterations. In this study, we aimed to provide an overall description of the mutational landscape in non-small cell lung cancer (NSCLC) using publicly available sequencing data.

Methods

We used the American Association for Cancer Research’s Project Genomics Evidence Neoplasia Information Exchange (GENIE) [GENIE Cohort v11.0-public study] to obtain sequencing data for patients diagnosed with NSCLC. Mutational profiles were described according to race (White, Black, or Asian) and histopathology (adenocarcinoma or squamous cell carcinoma). We used the OncoKB to assess the actionability of frequently mutated genes in the studied cohort.

Results

We included 16,498 samples (13,927 White, 1,304 Black, and 1,267 Asian; 12,790 adenocarcinoma, and 1,546 squamous cell carcinoma). TP53 was the most frequently mutated gene, with half of the analyzed samples (49.6%) containing at least one TP53-related molecular alteration. TP53 mutation rate was higher in cases with squamous cell carcinoma compared to cases with adenocarcinoma (76.7% vs. 45.6%; p<0.001). In race-dependent subgroup analysis, mutations in EGFR gene occurred in about 53.3% of Asian cases to rank as the most frequently mutated gene in this subgroup (Table). Most of the frequently mutated genes in NSCLC (especially in the squamous cell carcinoma subgroup) are still not actionable (Table). Table: 418P

Commonly mutated genes in NSCLC

* gene with actionable mutation(s)

Conclusions

Despite progress in the targetability of NSCLC, many of the most frequently mutated genes are still not actionable. Genomic profiling has the potential to identify potential targets of interest, which could guide individualized treatment plans to address the current high burden of NSCLC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.