Localized and disseminated histiocytic sarcoma complex: A canine model

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Canine histiocytic sarcoma is an aggressive and uniformly-fatal round-cell neoplasm. The localized, peri-articular form of the disease (PAHS) appears to have statistically significant prolonged survival, when compared to the non - peri-articular form of the disease (non-PAHS). Knowledge of the molecular basis for the aggressiveness of the canine histiocytic sarcoma is foundational for developing effective treatments. The aim of this study was to characterize the molecular expression profiles of the different sub-types of the disease. Canine patients, with spontaneously-arising histiocytic sarcoma, were recruited for the study. Tumor tissue samples and peripheral blood were obtained and used for primary cell line development and gene expression analysis. Eight PAHS and 8 non-PAHS tumor samples were selected. RNA extraction, amplification and labeling were performed using standard techniques. Raw gene expression values were obtained using the Affymetrix GeneChip Canine Genome 2.0 Array. Background correction, normalization, PM correction, summarization, and expression analysis were performed using R/affy/limma. Gene set analysis was performed using BRB-ArrayTools, and the Molecular Signatures Database (MSigDB), to investigate gene ontology groups of genes whose expression was differentially regulated. Primary cell lines from tumor biopsies and peripheral blood samples were developed and characterized based on cellular morphology, growth characteristics, and immunophenotyping. In our gene expression array experiments, we identified specific gene transcripts that are more likely to represent true and biologically meaningful differences in expression levels between PAHS and non-PAHS. More specifically, metallopeptidase genes, and homeobox domain gene expression levels were enriched in the PAHS group, while ATP-binding cassette genes, and interleukin 1 receptor signaling gene expression levels were enriched in the non-PAHS group. Our results suggest presence of gene expression signatures that can provide insight in the diverse biologic behavior of the disease and highlight canine spontaneous tumors in understanding tumor biology. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5092. doi:1538-7445.AM2012-5092