title: Enriched transcription factor signatures in triple negative breast cancer indicates possible targeted therapies with existing drugs.
abstract: OBJECTIVE
  Triple negative (TN) breast cancers which lack expression of the estrogen (ER), progesterone (PR), and human epidermal growth factor 2 (HER2) receptors convey a poor prognosis due in part to a lack of targeted therapies.
  
  
  METHODS
  To identify viable targets for the treatment of TN disease, we have conducted a gene set enrichment analysis (GSEA) on seven different breast cancer whole genome gene expression cohorts comparing TN vs. ER + HER2 - to identify consistently enriched genes that share a common promoter motif. The seven cohorts were profiled on three different genome expression platforms (Affymetrix, Illumina and RNAseq) consisting in total of 2088 samples with IHC metadata.
  
  
  RESULTS
  GSEA identified enriched gene expression patterns in TN samples that share common promoter motifs associated with SOX9, E2F1, HIF1A, HMGA1, MYC BACH2, CEBPB, and GCNF/NR6A1. Unexpectedly, NR6A1 an orphan nuclear receptor normally expressed in germ cells of gonads is highly expressed in TN and ER + HER2 - samples making it an ideal drug target.
  
  
  CONCLUSIONS
  With the increasing number of large sample size breast cancer cohorts, an exploratory analysis of genes that are consistently enriched in TN sharing common promoter motifs allows for the identification of possible therapeutic targets with extensive validation in patient derived data sets.
authors.affiliation: Avera Cancer Institute, Sioux Falls, SD, United States.
authors.forename: Scooter
authors.initials: S
authors.lastname: Willis
authors.affiliation: Avera Cancer Institute, Sioux Falls, SD, United States.
authors.forename: Pradip
authors.initials: P
authors.lastname: De
authors.affiliation: Avera Cancer Institute, Sioux Falls, SD, United States.
authors.forename: Nandini
authors.initials: N
authors.lastname: Dey
authors.affiliation: The Scripps Research Institute, Jupiter, FL, United States.
authors.forename: Bradley
authors.initials: B
authors.lastname: Long
authors.affiliation: Avera Cancer Institute, Sioux Falls, SD, United States.
authors.forename: Brandon
authors.initials: B
authors.lastname: Young
authors.affiliation: Montefiore Medical Center, Bronx, NY, United States.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Sparano
authors.affiliation: Dana Farber Cancer Institute, Boston, MA, United States.
authors.forename: Victoria
authors.initials: V
authors.lastname: Wang
authors.affiliation: University of Pittsburgh Cancer Institute and UPMC Cancer Center, Pittsburgh, PA, United States.
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Davidson
authors.affiliation: Avera Cancer Institute, Sioux Falls, SD, United States.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Leyland-Jones
keywords: Breast cancer; ER +; GSEA; NR6A1; Triple negative