Abstract 1603: Primary breast cancer xenografts maintain the molecular profiles of corresponding patients’ tumors and recapitulate a part of stroma microenvironment

Abstract

Abstract Identifying new therapeutic agents for breast cancer (BC) treatment requires preclinical models that recapitulate the molecular characteristics of their respective clinical tumors. In this work, we analyzed the genomic and expression profiles of human BC xenografts and their corresponding patient's tumors. Eighteen BC xenografts were obtained by grafting tumor fragments from patients into Swiss nude mice. The molecular characterization of patient's and xenograft's tumors (early and late in vivo passages) was performed by DNA copy number analysis (aCGH) and gene expression analysis using Affymetrix Microarrays. Comparison of genomic profiles of BC xenografts with those of respective patient's tumors, showed a correlation coefficient higher than 0.50 in 14/18 paired tumors. Unsupervised hierarchical clustering analysis showed that 16/18 pairs segregated together further indicating the striking similarity between pairs. At the level of gene expression profile few variations were found between patient's tumor and their respective xenografts, i.e. 371 genes that were differentially expressed in more than 84% of paired tumors and that largely represent human stromal compartment related genes. Furthermore, analysis of gene expression by murine stroma revealed a partial but significant recapitulation of the primitive human stroma. Finally, we found that sequential mouse to mouse tumor passages did not affect neither genomic rearrangements nor gene expression profiles, suggesting a striking genetic stability of these models across the time. In conclusions, this panel of human BC xenografts accurately maintains the genomic and the expression profiles of their corresponding patient's tumors and are stable across sequential in vivo passages. Consequently, these xenografts represent a validated model for preclinical investigation of new therapeutic agents. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1603. doi:10.1158/1538-7445.AM2011-1603