title: Gene expression profiles of breast biopsies from healthy women identify a group with claudin-low features.
abstract: BACKGROUND
  Increased understanding of the variability in normal breast biology will enable us to identify mechanisms of breast cancer initiation and the origin of different subtypes, and to better predict breast cancer risk.
  
  
  METHODS
  Gene expression patterns in breast biopsies from 79 healthy women referred to breast diagnostic centers in Norway were explored by unsupervised hierarchical clustering and supervised analyses, such as gene set enrichment analysis and gene ontology analysis and comparison with previously published genelists and independent datasets.
  
  
  RESULTS
  Unsupervised hierarchical clustering identified two separate clusters of normal breast tissue based on gene-expression profiling, regardless of clustering algorithm and gene filtering used. Comparison of the expression profile of the two clusters with several published gene lists describing breast cells revealed that the samples in cluster 1 share characteristics with stromal cells and stem cells, and to a certain degree with mesenchymal cells and myoepithelial cells. The samples in cluster 1 also share many features with the newly identified claudin-low breast cancer intrinsic subtype, which also shows characteristics of stromal and stem cells. More women belonging to cluster 1 have a family history of breast cancer and there is a slight overrepresentation of nulliparous women in cluster 1. Similar findings were seen in a separate dataset consisting of histologically normal tissue from both breasts harboring breast cancer and from mammoplasty reductions.
  
  
  CONCLUSIONS
  This is the first study to explore the variability of gene expression patterns in whole biopsies from normal breasts and identified distinct subtypes of normal breast tissue. Further studies are needed to determine the specific cell contribution to the variation in the biology of normal breasts, how the clusters identified relate to breast cancer risk and their possible link to the origin of the different molecular subtypes of breast cancer.
authors: Dept of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Norway.
authors: Vilde D
authors: VD
authors: Haakensen
authors: Ole Christian
authors: OC
authors: Lingjaerde
authors: Torben
authors: T
authors: Lüders
authors: Margit
authors: M
authors: Riis
authors: Aleix
authors: A
authors: Prat
authors: Melissa A
authors: MA
authors: Troester
authors: Marit M
authors: MM
authors: Holmen
authors: Jan Ole
authors: JO
authors: Frantzen
authors: Linda
authors: L
authors: Romundstad
authors: Dina
authors: D
authors: Navjord
authors: Ida K
authors: IK
authors: Bukholm
authors: Tom B
authors: TB
authors: Johannesen
authors: Charles M
authors: CM
authors: Perou
authors: Giske
authors: G
authors: Ursin
authors: Vessela N
authors: VN
authors: Kristensen
authors: Anne-Lise
authors: AL
authors: Børresen-Dale
authors: Aslaug
authors: A
authors: Helland
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D015992:Body Mass Index; D001940:Breast / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D057167:Claudins / Q000378:metabolism*; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006262:Health; D006801:Humans; D008875:Middle Aged
chemical_list: D057167:Claudins