Associations of Two-Pore Domain Potassium Channels and Triple Negative Breast Cancer Subtype in the Cancer Genome Atlas: Systematic Evaluation of Gene Expression and Methylation

Details

• Personal Author:
  Argos M ; Dookeran KA ; Stayner L ; Zhang W
• Description:
  Objectives: It is unclear whether 2-pore domain potassium channels are novel molecular markers with differential expression related to biologically aggressive triple-negative type breast tumors. Our objective was to systematically evaluate associations of 2-pore domain potassium channel gene expression and DNA methylation with triplenegative subtype in The Cancer Genome Atlas invasive breast cancer dataset. Methylation and expression data for all fifteen 2-pore domain potassium family genes were examined for 1040 women, and associations with triple-negative subtype (vs. luminal A) were evaluated using age/race adjusted generalized-linear models, with Bonferroni-corrected significance thresholds. Subtype associated CpG loci were evaluated for functionality related to expression using Spearman's correlation. Results: Overexpression of KCNK5, KCNK9 and KCNK12, and underexpression of KCNK6 and KCNK15, were significantly associated with triple-negative subtype (Bonferroni-corrected p < 0.0033). A total of 195 (114 hypomethylated and 81 hypermethylated) CpG loci were found to be significantly associated with triple-negative subtype (Bonferronicorrected p < 8.22 × 10 8). Significantly negatively correlated expression patterns that were differentially observed in triple-negative vs. luminal A subtype were demonstrated for: KCNK2 (gene body: cg04923840, cg13916421), KCNK5 (gene body: cg05255811, cg18705155, cg09130674, cg21388745, cg00859574) and KCNK9 (TSS1500: cg21415530, cg12175729; KCNK9/TRAPPC9 intergenic region: cg17336929, cg25900813, cg03919980). CpG loci listed for KCNK5 and KCNK9 all showed relative hypomethylation for probability of triple-negative vs. luminal A subtype. Triple-negative subtype was associated with distinct 2-pore domain potassium channel expression patterns. Both KCNK5 and KCNK9 overexpression appeared to be functionally related to CpG loci hypomethylation. [Description provided by NIOSH]
• Subjects:
  Aging Genetics Neoplasms Occupational Health Race Factors Safety Women
• Keywords:
  Age Groups Author Keywords: Potassium Channels Biological Effects Biological Function Breast Cancer Cancer Cell Function Cellular Function Deoxyribonucleic Acids DNA Genes Humans Models Molecular Biology Potassium Potassium Compounds Racial Factors Subtype TCGA

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• ISSN:
  1756-0500
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Illinois ; OSHA Region 5 ; Wisconsin
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  10
• NIOSHTIC Number:
  nn:20051641
• Citation:
  BMC Res Notes 2017 Sep; 10:475
• Contact Point Address:
  Keith A. Dookeran, Epidemiology, University of Wisconsin-Milwaukee, Joseph J. Zilber School of Public Health, 1240 N. 10th St, Milwaukee, WI 53205
• Email:
  dookeran@uwm.edu
• CAS Registry Number:
  Potassium (CAS RN 7440-09-7)
• Federal Fiscal Year:
  2017
• Performing Organization:
  University of Illinois at Chicago
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  BMC Research Notes
• End Date:
  20290630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:794522ebf5f53c170b2ab486cd6ecbdc9f9f142a3e1706d15f25affe08b4de74fdc858247a42b15a62ee5f1839f6aa25ff4363c5d33b2834350c685e445b8c06
• Download URL:
  https://stacks.cdc.gov/view/cdc/211498/cdc_211498_DS1.pdf
• File Type:
  [PDF - 1022.49 KB ]