K. Loo1, I. Soliman1, M. Renzetti1, T. Li1, H. Wu1, B. Luo1, A. Olszanski1, S. Movva1, M. Lango1, N. Goel1, S. Reddy1, J. Farma1 1Fox Chase Cancer Center,Philadelphia, PA, USA
Introduction: The use of molecular profiling to characterize tumors is becoming increasingly utilized to guide and tailor therapies for personalized treatment in the setting of malignant melanoma. Furthermore, smoking has been identified as a largely preventable cause of cancer mortality. Yet it remains to be seen whether smoking has a causative or protective effect in the setting of malignant melanoma. Using Next Generation Sequencing (NGS), we investigated a panel of 50 targetable cancer-related gene mutations in melanoma tumors. The principle aim of this study was to investigate the correlations between previous history of smoking with genetic mutations among individual genes, as well as total mutation burden in patients with malignant melanoma.
Methods: A retrospective study was conducted to include both primary and recurrent malignant melanoma tumor samples. Utilizing a prospective database, we identified a cohort of patients whose tumor tissue samples underwent NGS sequencing analysis for somatic mutations of 50 cancer-related genes. Within this cohort, clinical and pathological data were also collected. A univariate analysis was conducted using Fisher’s exact and Wilcoxon tests to compare patients with previous history of smoking to never smokers to investigate differences in each cohort’s molecular profile.
Results: A total of 173 patients with malignant melanoma whose tumor tissue specimens underwent NGS sequencing were analyzed in this study cohort. Median age at diagnosis was 65 (range 21-94) and 64% were male (n=111). The smoking cohort was divided into never smokers (n=72) versus current or former smokers (n=101). Of the 168 patients with staging data, 9% of patients were Stage I melanoma (n=15), 30% Stage II (n=50), 49% with Stage III (n=83), and 12%with Stage IV (n=20).
In the total cohort, 277 mutations were identified affecting 34 unique genes. No mutations were found in 12% of patients (n=20), while 47% of patients (n=82) had 1 mutation, 24% (n=41) had 2 mutations, 9% (n=16) had 3 mutations, and 8% (n=14) had 4 or more mutations. The most common mutations among patients with a history of smoking were BRAF v600E (27.7%, vs. 19.4% in never smokers) and CDKN2A (12.87%, vs. 9.72% in never smokers) genes. Conversely, the most common genes among never smokers were NRAS (34.72%, vs. 31.7% in smokers) and TP53 (22.22%, vs. 21.8% in smokers). The overall mutation burden in the never smoker cohort was 1.59 versus 1.60 in the current and former smoker cohort (p=0.94).
Conclusion: This study demonstrated no significant association of overall mutational burden or increased incidence of individual gene mutations to smoking status, additional studies are needed to identify the effect of smoking on melanoma tumor characteristics with a larger sample size. Further studies with additional tumor biomarkers are additionally warranted to discern the impact of smoking on malignant melanoma tumors.