Whole Exome Profiling of NSCLC Among African Americans

Ryan, B. M.; Pine, S. R.; Byun, J. S.; Tandon, M.; Arauz, R. F.; Sinha, S.; Napoles, A. M.; Mitchell, Khadijah; Perez-Stable, E. J.; Zingone, A.; Gardner, K.; Taylor, S.; Kuhn, S.

Whole Exome Profiling of NSCLC Among African Americans

Abstract

Introduction: Lung cancer incidence is higher among African Americans (AAs) compared with European Americans (EAs) in the United States, especially among men. Although significant progress has been made profiling the genomic makeup of lung cancer in EAs, AAs continue to be underrepresented. Our objective was to chart the genome-wide landscape of somatic mutations in lung cancer tumors from AAs.

Methods: In this study, we used the whole-exome sequencing of 82 tumor and noninvolved tissue pairs from AAs. Patients were selected from an ongoing casecontrol study conducted by the National Cancer Institute and the University of Maryland.

Results: Among all samples, we identified 178 significantly mutated genes (p < 0.05), five of which passed the threshold for false discovery rate (p < 0.1). In lung adenocarcinoma (LUAD) tumors, mutation rates in STK11 (p = 0.05) and RB1 (p = 0.008) were significantly higher in AA LUAD tumors (25% and 13%, respectively) compared with The Cancer Genome Atlas EA samples (14% and 4%, respectively). In squamous cell carcinomas, mutation rates in STK11 (p = 0.002) were significantly higher among AA (8%) than EA tumors from The Cancer Genome Atlas (1%). Integrated somatic mutation data with CIBERSORT (Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts) data analysis revealed LUAD tumors from AAs carrying STK11 mutations have decreased interferon signaling.

Conclusions: Although a considerable degree of the somatic mutation landscape is shared between EAs and AAs, discrete differences in mutation frequency in potentially important oncogenes and tumor suppressors exist. A better understanding of the molecular basis of lung cancer in AA patients and leveraging this information to guide clinical interventions may help reduce disparities. Published by Elsevier Inc. on behalf of International Association for the Study of Lung Cancer.

Title	Whole Exome Profiling of NSCLC Among African Americans
Creator	Ryan, B. M.
	Pine, S. R.
	Byun, J. S.
	Tandon, M.
	Arauz, R. F.
	Sinha, S.
	Napoles, A. M.
	Mitchell, Khadijah
	Perez-Stable, E. J.
	Zingone, A.
	Gardner, K.
	Taylor, S.
	Kuhn, S.
Publisher	Journal of Thoracic Oncology
Academic Department	Biology
Division	Natural Sciences
Organization	Lafayette College
Date Issued	December 2020
Date Available	2022-05-12
Type	Article
Language	English
Keyword	Whole exome sequencing
	NSCLC
	Health disparity
	lung cancer
Bibliographic Citation	Arauz, R. F. (2020 Dec) "Whole Exome Profiling of NSCLC Among African Americans." Journal of Thoracic Oncology 15 (12): 1880-1892
Standard Identifier	DOI 10.1016/j.jtho.2020.08.029
Standard Identifier	Handle 10385/sb397964n
Permalink	http://hdl.handle.net/10385/sb397964n
Rights Statement	In Copyright