title: Bone marrow stromal antigen 2 (BST-2) DNA is demethylated in breast tumors and breast cancer cells.
abstract: BACKGROUND
  Bone marrow stromal antigen 2 (BST-2) is a known anti-viral gene that has been recently identified to be overexpressed in many cancers, including breast cancer. BST-2 is critical for the invasiveness of breast cancer cells and the formation of metastasis in vivo. Although the regulation of BST-2 in immune cells is unraveling, it is unknown how BST-2 expression is regulated in breast cancer. We hypothesized that meta-analyses of BST-2 gene expression and BST-2 DNA methylation profiles would illuminate mechanisms regulating elevated BST-2 expression in breast tumor tissues and cells.
  
  
  METHODS
  We performed comprehensive meta-analyses of BST-2 gene expression and BST-2 DNA methylation in The Cancer Genome Atlas (TCGA) and various Gene Expression Omnibus (GEO) datasets. BST-2 expression levels and BST-2 DNA methylation status at specific CpG sites on the BST-2 gene were compared for various breast tumor molecular subtypes and breast cancer cell lines.
  
  
  RESULTS
  We show that BST-2 gene expression is inversely associated with the methylation status at specific CpG sites in primary breast cancer specimens and breast cancer cell lines. BST-2 demethylation is significantly more prevalent in primary tumors and cancer cells than in normal breast tissues or normal mammary epithelial cells. Demethylation of the BST-2 gene significantly correlates with its mRNA expression. These studies provide the initial evidence that significant differences exist in BST-2 DNA methylation patterns between breast tumors and normal breast tissues, and that BST-2 expression patterns in tumors and cancer cells correlate with hypomethylated BST-2 DNA.
  
  
  CONCLUSIONS
  Our study suggests that the DNA methylation pattern and expression of BST-2 may play a role in disease pathogenesis and could serve as a biomarker for the diagnosis of breast cancer.
authors: Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America; Interdisciplinary Graduate program in Molecular and Cellular Biology (MCB), University of Iowa, Iowa City, Iowa, United States of America.
authors: Wadie D
authors: WD
authors: Mahauad-Fernandez
authors: Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America; Medical Scientist Training Program, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.
authors: Nicholas C
authors: NC
authors: Borcherding
authors: Interdisciplinary Graduate program in Molecular and Cellular Biology (MCB), University of Iowa, Iowa City, Iowa, United States of America; Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America; Medical Scientist Training Program, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.
authors: Weizhou
authors: W
authors: Zhang
authors: Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America; Interdisciplinary Graduate program in Molecular and Cellular Biology (MCB), University of Iowa, Iowa City, Iowa, United States of America.
authors: Chioma M
authors: CM
authors: Okeoma
mesh_terms: D015703:Antigens, CD / Q000235:genetics*; D001374:Azacitidine / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D019295:Computational Biology; D018899:CpG Islands; D019175:DNA Methylation; D030561:Databases, Nucleic Acid; D057890:Epigenomics; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D015703:Antigens, CD; D001374:Azacitidine; D058851:GPI-Linked Proteins; D012333:RNA, Messenger; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2