title: Molecular profiling of patient-derived breast cancer xenografts.
abstract: BACKGROUND
  Identification of new therapeutic agents for breast cancer (BC) requires preclinical models that reproduce the molecular characteristics of their respective clinical tumors. In this work, we analyzed the genomic and gene expression profiles of human BC xenografts and the corresponding patient tumors.
  
  
  METHODS
  Eighteen BC xenografts were obtained by grafting tumor fragments from patients into Swiss nude mice. Molecular characterization of patient tumors and xenografts was performed by DNA copy number analysis and gene expression analysis using Affymetrix Microarrays.
  
  
  RESULTS
  Comparison analysis showed that 14/18 pairs of tumors shared more than 56% of copy number alterations (CNA). Unsupervised hierarchical clustering analysis showed that 16/18 pairs segregated together, confirming the similarity between tumor pairs. Analysis of recurrent CNA changes between patient tumors and xenografts showed losses in 176 chromosomal regions and gains in 202 chromosomal regions. Gene expression profile analysis showed that less than 5% of genes had recurrent variations between patient tumors and their respective xenografts; these genes largely corresponded to human stromal compartment genes. Finally, analysis of different passages of the same tumor showed that sequential mouse-to-mouse tumor grafts did not affect genomic rearrangements or gene expression profiles, suggesting genetic stability of these models over time.
  
  
  CONCLUSIONS
  This panel of human BC xenografts maintains the overall genomic and gene expression profile of the corresponding patient tumors and remains stable throughout sequential in vivo generations. The observed genomic profile and gene expression differences appear to be due to the loss of human stromal genes. These xenografts, therefore, represent a validated model for preclinical investigation of new therapeutic agents.
authors.affiliation: Translational Research Department, Institut Curie, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Reyal
authors.forename: Charlotte
authors.initials: C
authors.lastname: Guyader
authors.forename: Charles
authors.initials: C
authors.lastname: Decraene
authors.forename: Carlo
authors.initials: C
authors.lastname: Lucchesi
authors.forename: Nathalie
authors.initials: N
authors.lastname: Auger
authors.forename: Franck
authors.initials: F
authors.lastname: Assayag
authors.forename: Ludmilla
authors.initials: L
authors.lastname: De Plater
authors.forename: David
authors.initials: D
authors.lastname: Gentien
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Poupon
authors.forename: Paul
authors.initials: P
authors.lastname: Cottu
authors.forename: Patricia
authors.initials: P
authors.lastname: De Cremoux
authors.forename: Pierre
authors.initials: P
authors.lastname: Gestraud
authors.forename: Anne
authors.initials: A
authors.lastname: Vincent-Salomon
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Fontaine
authors.forename: Sergio
authors.initials: S
authors.lastname: Roman-Roman
authors.forename: Olivier
authors.initials: O
authors.lastname: Delattre
authors.forename: Didier
authors.initials: D
authors.lastname: Decaudin
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Marangoni
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D016000:Cluster Analysis; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005260:Female; D042822:Genomic Instability; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D014183:Transplantation, Heterologous
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human