title: A core MYC gene expression signature is prominent in basal-like breast cancer but only partially overlaps the core serum response.
abstract: BACKGROUND
  The MYC oncogene contributes to induction and growth of many cancers but the full spectrum of the MYC transcriptional response remains unclear.
  
  
  RESULTS
  Using microarrays, we conducted a detailed kinetic study of genes that respond to MYCN or MYCNDeltaMBII induction in primary human fibroblasts. In parallel, we determined the response to steady state overexpression of MYCN and MYCNDeltaMBII in the same cell type. An overlapping set of 398 genes from the two protocols was designated a 'Core MYC Signature' and used for further analysis. Comparison of the Core MYC Signature to a published study of the genes induced by serum stimulation revealed that only 7.4% of the Core MYC Signature genes are in the Core Serum Response and display similar expression changes to both MYC and serum. Furthermore, more than 50% of the Core MYC Signature genes were not influenced by serum stimulation. In contrast, comparison to a panel of breast cancers revealed a strong concordance in gene expression between the Core MYC Signature and the basal-like breast tumor subtype, which is a subtype with poor prognosis. This concordance was supported by the higher average level of MYC expression in the same tumor samples.
  
  
  CONCLUSIONS
  The Core MYC Signature has clinical relevance as this profile can be used to deduce an underlying genetic program that is likely to contribute to a clinical phenotype. Therefore, the presence of the Core MYC Signature may predict clinical responsiveness to therapeutics that are designed to disrupt MYC-mediated phenotypes.
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Chandriani
authors.forename: Eirik
authors.initials: E
authors.lastname: Frengen
authors.forename: Victoria H
authors.initials: VH
authors.lastname: Cowling
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Pendergrass
authors.forename: Charles M
authors.initials: CM
authors.lastname: Perou
authors.forename: Michael L
authors.initials: ML
authors.lastname: Whitfield
authors.forename: Michael D
authors.initials: MD
authors.lastname: Cole
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D016259:Genes, myc; D006801:Humans; D007150:Immunohistochemistry; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis
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