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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 triple-negative 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 (Bonferroni-corrected 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.    Electronic supplementary material  The online version of this article (doi:10.1186/s13104-017-2777-4) contains supplementary material, which is available to authorized users.

bmc research notes

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