Molecular Profiling of Patient-derived Breast Cancer Xenografts

Overview

Journal Breast Cancer Res

Specialty Oncology

Date 2012 Jan 18

PMID 22247967

Citations 96

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

Affiliations

Soon will be listed here.

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.

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