title: Molecular profiling of breast cancer cell lines defines relevant tumor models and provides a resource for cancer gene discovery.
abstract: BACKGROUND
  Breast cancer cell lines have been used widely to investigate breast cancer pathobiology and new therapies. Breast cancer is a molecularly heterogeneous disease, and it is important to understand how well and which cell lines best model that diversity. In particular, microarray studies have identified molecular subtypes-luminal A, luminal B, ERBB2-associated, basal-like and normal-like-with characteristic gene-expression patterns and underlying DNA copy number alterations (CNAs). Here, we studied a collection of breast cancer cell lines to catalog molecular profiles and to assess their relation to breast cancer subtypes.
  
  
  METHODS
  Whole-genome DNA microarrays were used to profile gene expression and CNAs in a collection of 52 widely-used breast cancer cell lines, and comparisons were made to existing profiles of primary breast tumors. Hierarchical clustering was used to identify gene-expression subtypes, and Gene Set Enrichment Analysis (GSEA) to discover biological features of those subtypes. Genomic and transcriptional profiles were integrated to discover within high-amplitude CNAs candidate cancer genes with coordinately altered gene copy number and expression.
  
  
  RESULTS
  Transcriptional profiling of breast cancer cell lines identified one luminal and two basal-like (A and B) subtypes. Luminal lines displayed an estrogen receptor (ER) signature and resembled luminal-A/B tumors, basal-A lines were associated with ETS-pathway and BRCA1 signatures and resembled basal-like tumors, and basal-B lines displayed mesenchymal and stem/progenitor-cell characteristics. Compared to tumors, cell lines exhibited similar patterns of CNA, but an overall higher complexity of CNA (genetically simple luminal-A tumors were not represented), and only partial conservation of subtype-specific CNAs. We identified 80 high-level DNA amplifications and 13 multi-copy deletions, and the resident genes with concomitantly altered gene-expression, highlighting known and novel candidate breast cancer genes.
  
  
  CONCLUSIONS
  Overall, breast cancer cell lines were genetically more complex than tumors, but retained expression patterns with relevance to the luminal-basal subtype distinction. The compendium of molecular profiles defines cell lines suitable for investigations of subtype-specific pathobiology, cancer stem cell biology, biomarkers and therapies, and provides a resource for discovery of new breast cancer genes.
authors: Department of Pathology, Stanford University, Stanford, CA, USA.
authors: Jessica
authors: J
authors: Kao
authors: Keyan
authors: K
authors: Salari
authors: Melanie
authors: M
authors: Bocanegra
authors: Yoon-La
authors: YL
authors: Choi
authors: Luc
authors: L
authors: Girard
authors: Jeet
authors: J
authors: Gandhi
authors: Kevin A
authors: KA
authors: Kwei
authors: Tina
authors: T
authors: Hernandez-Boussard
authors: Pei
authors: P
authors: Wang
authors: Adi F
authors: AF
authors: Gazdar
authors: John D
authors: JD
authors: Minna
authors: Jonathan R
authors: JR
authors: Pollack
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D017931:DNA Primers; D005260:Female; D020869:Gene Expression Profiling; D019398:Genes, BRCA1; D006801:Humans; D007150:Immunohistochemistry; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger