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Whole Exome Profiling of NSCLC Among African Americans

  1. Author:
    Arauz, Rony F
    Byun, Jung S
    Tandon,Mayank
    Sinha, Sanju
    Kuhn,Skyler
    Taylor, Sheryse
    Zingone, Adriana
    Mitchell, Khadijah A
    Pine, Sharon R
    Gardner, Kevin
    Perez-Stable, Eliseo J
    Napoles, Anna M
    Ryan, Bríd M

  2. Author Address

    Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892., Division of Intramural Research, National Institute on Minority Health and Health Disparities, Bethesda, MD 20892; Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD., CCR Collaborative Bioinformatics Resource CCBR, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892; Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research, Frederick, MD 21702., Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892; Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892., Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ 08854., National Institute of Minority Health and Health Disparities, Bethesda, MD 20892; Columbia University Medical Center, Columbia University, New York, NY, 10027., National Institute of Minority Health and Health Disparities, Bethesda, MD 20892., Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892. Electronic address: Brid.Ryan@nih.gov.,
    1. Year: 2020
    2. Date: DEC
    3. Epub Date: 2020 09 12
  2. Journal: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
    1. 15
    2. 12
    3. Pages: 1880-1892
  4. Type of Article: Article
  5. ISSN: 1556-0864
  1. Abstract:

    Introduction: Lung cancer incidence is higher among African Americans (AAs) compared with European Americans (EAs) in the United States, especially among men. While 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 African Americans. Methods: In this study, we used whole exome sequencing (WES) of 82 tumor and non-involved tissue pairs from AAs. Patients were selected from an ongoing case-control study conducted by the NCI 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 (FDR 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 TCGA 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 TCGA (1%). Integrated somatic mutation data with CIBERSORT data analysis revealed LUAD tumors from AAs carrying STK11 mutations have decreased interferon signaling. Conclusions: While 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. Better understanding of the molecular basis of lung cancer in AA patients and leveraging this information to guide clinical interventions may help reduce disparities. Keywords: NSCLC; health disparity; lung cancer; whole exome sequencing. Published by Elsevier Inc.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.jtho.2020.08.029
  3. PMID: 32931935
  4. View record in Web of Science®
  5. WOS: 000610074500018
  6. PII : S1556-0864(20)30721-8

Library Notes

  1. Fiscal Year: FY2020-2021
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