Detection of novel lung cancer mutational signatures in African Americans

Authors

• N Nichols
• KA Mitchell
• J Waterfall
• D Edelman
• A Zingone
• E Bowman
• P Meltzer
• BM Ryan

Abstract

African Americans (AA) have a higher lung cancer incidence and mortality compared to all other racial groups in the US. Advances in NGS technology are guiding how we investigate and treat lung cancer, though most studies are conducted on populations of European ancestry. To date, few studies have profiled the somatic landscape of lung cancer in AA and those that have, yielded, at times, disparate results. Herein, we leveraged the ONCOVAR platform to assess the somatic mutation profile in 564 cancer associated genes in 130 African Americans. The first filtering step identified 4,091 mutations. The second filtering step, which separates candidate drivers from passenger mutations, identified 1,456 mutations. The mean number of number of somatic mutations per patient was 35.9 (range of 0-426). The mean number of candidate driver mutations was 12.8 (range 0-132). Twenty-one patients did not have any candidate driver mutations from the mutation panel. KRAS mutations are lower in AA. Also, while TP53 mutation frequency is similar, the specific mutated codons are different. Moreover, we also identified a high prevalence of PTPRT and JAK2 mutations. These genes are key in the IL-6/STAT3/miR-21 axis—indeed, patients with mutated PTPRT had increased miR-21 expression. We observed that the total number of mutations among menthol cigarette smokers were higher than among non-menthol cigarette smokers. Menthol cigarette smoking is the key factor that distinguishes AA smokers from EA smokers, therefore this finding warrants further follow up. Moreover, we also identified mutational signatures distinctly found in tumors from menthol smokers.

Scientific Focus Area: Health Disparities

This page was last updated on Friday, March 26, 2021