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Series GSE23760 Query DataSets for GSE23760
Status Public on Aug 24, 2010
Title Gene Expression Profiling Identifies Inflammation and Angiogenesis as Distinguishing Features of Canine Hemangiosarcoma
Organism Canis lupus familiaris
Experiment type Expression profiling by array
Summary Background
The etiology of hemangiosarcoma remains incompletely understood. Its common occurrence in dogs suggests predisposing factors favor its development in this species. These factors could represent a constellation of heritable characteristics that promote transformation events and/or facilitate the establishment of a microenvironment that is conducive for survival of malignant blood vessel-forming cells. The hypothesis for this study was that characteristic molecular features distinguish hemangiosarcoma from non-malignant endothelial cells, and that such features are informative for the etiology of this disease.
We first investigated mutations of VHL and Ras family genes that might drive hemangiosarcoma by sequencing tumor DNA and mRNA (cDNA). Protein expression was examined using immunoblotting. Next, we evaluated genome-wide gene expression profiling using the Affymetrix Canine 2.0 platform as a global approach to test the hypothesis. Data were evaluated using routine bioinformatics and validation was done using quantitative real time RT-PCR.
Each of 10 tumor and four non-tumor samples analyzed had wild type sequences for these genes. At the genome wide level, hemangiosarcoma cells clustered separately from non-malignant endothelial cells based on a robust signature that included genes involved in inflammation, angiogenesis, adhesion, invasion, metabolism, cell cycle, signaling, and patterning. This signature did not simply reflect a cancer-associated angiogenic phenotype, as it also distinguished hemangiosarcoma from non-endothelial, moderately to highly angiogenic bone marrow-derived tumors (lymphoma, leukemia, osteosarcoma).
The data show that inflammation and angiogenesis are important processes in the pathogenesis of vascular tumors, but a definitive ontogeny of the cells that give rise to these tumors remains to be established. The data do not yet distinguish whether functional or ontogenetic plasticity creates this phenotype, although they suggest that cells which give rise to hemangiosarcoma modulate their microenvironment to promote tumor growth and survival. We propose that the frequent occurrence of canine hemangiosarcoma in defined dog breeds, as well as its similarity to homologous tumors in humans, offers unique models to solve the dilemma of stem cell plasticity and whether angiogenic endothelial cells and hematopoietic cells originate from a single cell or from distinct progenitor cells.

This SuperSeries is composed of the SubSeries listed below.
Overall design Refer to individual Series.
Citation(s) 21062482, 19461996
Submission date Aug 23, 2010
Last update date Dec 28, 2012
Contact name Beth Tamburini
Organization name University of Colorado Denver
Department Immunology
Street address 1400 Jackson Street, K503
City Denver
State/province CO
ZIP/Postal code 80206
Country USA
Platforms (1)
GPL3738 [Canine_2] Affymetrix Canine Genome 2.0 Array
Samples (44)
GSM377398 Golden Retriever, hemangiosarcoma: ChadG4
GSM377399 Golden Retriever, hemangiosarcoma: ChadG6
GSM377400 Golden Retriever, hemangiosarcoma: ChadG8
This SuperSeries is composed of the following SubSeries:
GSE15086 Gene Expression Profiles of Sporadic Canine Hemangiosarcoma are Uniquely Associated with Breed
GSE22129 Gene Expression Profiling Identifies Inflammation and Angiogenesis as Distinguishing Features of Canine Hemangiosarcoma
BioProject PRJNA130841

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Supplementary file Size Download File type/resource
GSE23760_RAW.tar 153.6 Mb (http)(custom) TAR (of CEL)

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