Comparative Gene Expression Analysis of Canine and Human Osteosarcoma
Tufts' Canine and Feline Breeding and Genetics Conference, 2005
Melissa Paoloni1, Sean Davis2, Sue Lana3, Steve Withrow3, Paul Meltzer2 and Chand Khanna1
1Comparative Oncology Program, Center for Cancer Research, National Cancer Institute; 2National Human Genome Research Institute, National Institutes of Health, Bethesda, MD; 3Animal Cancer Center, Colorado State University, Fort Collins, CO

Introduction: Canine osteosarcoma is a valuable model of pediatric osteosarcoma, validated at both a histological and biological level. The goal of this study was to characterize this model at the genomic level through a comparison of gene expression signatures of canine and pediatric osteosarcoma.

Methods: RNA was extracted from 15 canine and 15 pediatric primary osteosarcomas and selected normal canine and human tissues. Affymetrix oligonucleotide arrays representing dog (Dog Genome chip v1.0) and human (U133A Human chip) were used. Hierarchical clustering was performed on both species separately. Shared orthologues, represented on the arrays were normalized across species and then clustered. A preliminary dog gene list of interest was identified by subtraction of dog osteosarcoma genes from those expressed in normal tissues.

Results: Normalized cluster analysis of dog and human array data sets revealed a clear distinction between osteosarcoma and normal tissues. Mapping of overlapping genes between dog and human present on both array sets followed by pooled normalization yielded 7000-9000 genes for clustering of dog and human data sets. Interestingly two osteosarcoma clusters including both dog and human osteosarcoma samples were found. Highly expressed genes in canine osteosarcoma compared to canine normal tissues included genes associated with connective tissue, cell adhesion and extra-cellular matrix proteins.

Conclusions: This data demonstrates the strong similarity between canine and human osteosarcoma based on global gene expression. Ongoing evaluation will validate the biological similarity in gene expression between dog and human osteosarcoma and will define specific genes or pathways common and distinct in these species.

Speaker Information
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Melissa Paoloni
Comparative Oncology Program, Center for Cancer Research
National Cancer Institute

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