Gene Expression Profiles of Sporadic Canine Hemangiosarcoma Are Uniquely Associated with Breed

Abstract

The role an individual's genetic background plays on phenotype and biological behavior of sporadic tumors remains incompletely understood. We showed previously that lymphomas from Golden Retrievers harbor defined, recurrent chromosomal aberrations that occur less frequently in lymphomas from other dog breeds, suggesting spontaneous canine tumors provide suitable models to define how heritable traits influence cancer genotypes. Here, we report a complementary approach using gene expression profiling in a naturally occurring endothelial sarcoma of dogs (hemangiosarcoma). Naturally occurring hemangiosarcomas of Golden Retrievers clustered separately from those of non-Golden Retrievers, with contributions from transcription factors, survival factors, and from pro-inflammatory and angiogenic genes, and which were exclusively present in hemangiosarcoma and not in other tumors or normal cells (i.e., they were not due simply to variation in these genes among breeds). Vascular Endothelial Growth Factor Receptor 1 (VEGFR1) was among genes preferentially enriched within known pathways derived from gene set enrichment analysis when characterizing tumors from Golden Retrievers versus other breeds. Heightened VEGFR1 expression in these tumors also was apparent at the protein level and targeted inhibition of VEGFR1 increased proliferation of hemangiosarcoma cells derived from tumors of Golden Retrievers, but not from other breeds. Our results suggest heritable factors mold gene expression phenotypes, and consequently biological behavior in sporadic, naturally occurring tumors.

Aspectos epidemiológicos e anatomopatológicos do hemagiossarcoma em cães: 40 casos (1965-2012)

“…Em alguns estudos, há maior número de machos afetados (Culbertson 1982, Ward et al 1994, embora a maior parte dos autores não tenha relatado predisposição sexual (Kleine et al 1970, Hirsch et al 1981, Hargis et al 1992. A inϐluência hereditá-ria é bastante discutida por alguns autores, pois se acredita haver forte predisposição de cães das raças Pastor Alemão (Kleine et al 1970, Hirsch et al 1981, Brown et al 1985, Labrador Retriever (Schultheiss 2004) e Golden Retriever (Tamburini et al 2009). Neste estudo, a prevalência do tumor em cães da raça Pastor Alemão foi de 20%, semelhante à frequência encontrada por Kleine et al (1970).…”

Comparison of CD34, CD31, and Factor VIII–Related Antigen Immunohistochemical Expression in Feline Vascular Neoplasms and CD34 Expression in Feline Nonvascular Neoplasms

“…16 Alternatively, overexpression of some genes has been reported in some canine vascular neoplasms. 26 Despite the sensitive labeling of neoplastic endothelial cells with antibodies to CD34, many nonvascular (epithelial, mesenchymal, leukocytic, and melanocytic) neoplasms also had positive labeling for CD34. CD34 labeling has been Figure 2.…”

A retrospective study of cardiac hemangiosarcoma in dogs

“…Unfortunately, results of the cytological examination of the exudate, which was obtained during the pericardiocentesis, proved to be negative, which has been confirmed in this study. In echocardiographic examination, occasionally the tumor can be visualized, most frequently originating from the right atrium (1,6). The tumor is always strictly linked to myocardium and its structure is nonhomogeneous.…”

“…The etiology of hemangiosarcoma remains incompletely understood (1,2). It is the most frequently diagnosed primary tumor of the canine heart, but, because of low prevalence, only a few reviews about manifestation of this and other cardiac tumors are available (3).…”