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Lung cancer in African Americans is characterized by a histone modifying enzyme gene signature

Wednesday, September 16, 2015 — Poster Session I

3:30 p.m. – 5:00 p.m.
FAES Terrace
NCI
HEALTH-4

Authors

  • KA Mitchell
  • A Zingone
  • BM Ryan

Abstract

African Americans (AA) have the highest lung cancer incidence and mortality rates when compared with other populations. These racial disparities are not completely explained by tobacco smoking as AA smoke significantly less than European Americans (EA). This suggests that biological determinants are involved. We hypothesized that biological differences could act as signatures for various etiologies and exposures and be leveraged for translational purposes. Profiling the coding transcriptome of matched lung tumor and normal tissues using Affymetrix arrays and the non-coding transcriptome using NanoString arrays, followed by subsequent Gene Set Enrichment Analysis (GSEA) and Connectivity Mapping (CM), we identified distinct molecular phenotypes in AA tumors when compared with EA. In addition, genes specifically upregulated in prostate and breast tumors from AA compared with EA were also upregulated in lung tumors from AA, suggesting systematic differences in tumor biology by race. GSEA revealed a histone modifying enzyme signature that is positively enriched in lung tumors from AA and inversely enriched in EA. Furthermore, CM strongly suggested that lung tumors from AA and EA would have varying sensitivities to histone deacetylase inhibitors (HDACi). Population-specific cell lines confirmed these CM predictions. Moreover, histone deacetylases (HDACs) were found to be differentially expressed in AA tumors, suggesting a mechanistic basis for differential responses to HDACi treatment. Our study also found that miRNA signatures do not contribute to the differential gene expression signatures in lung cancer between AA and EA, and is the first to report HDAC tumor biology differs in lung cancers from AA and EA.

Category: Health Disparities