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Breast Cancer Research
Published in: Breast Cancer Research 1/2013

Open Access 01-02-2012 | Research article

Molecular profiling of patient-derived breast cancer xenografts

Authors: Fabien Reyal, Charlotte Guyader, Charles Decraene, Carlo Lucchesi, Nathalie Auger, Franck Assayag, Ludmilla De Plater, David Gentien, Marie-France Poupon, Paul Cottu, Patricia De Cremoux, Pierre Gestraud, Anne Vincent-Salomon, Jean-Jacques Fontaine, Sergio Roman-Roman, Olivier Delattre, Didier Decaudin, Elisabetta Marangoni

Published in: Breast Cancer Research | Issue 1/2013

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Abstract

Introduction

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.
Appendix
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Metadata
Title
Molecular profiling of patient-derived breast cancer xenografts
Authors
Fabien Reyal
Charlotte Guyader
Charles Decraene
Carlo Lucchesi
Nathalie Auger
Franck Assayag
Ludmilla De Plater
David Gentien
Marie-France Poupon
Paul Cottu
Patricia De Cremoux
Pierre Gestraud
Anne Vincent-Salomon
Jean-Jacques Fontaine
Sergio Roman-Roman
Olivier Delattre
Didier Decaudin
Elisabetta Marangoni
Publication date
01-02-2012
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2013
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr3095

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