The Two Main Forms of Histiocytic Sarcoma in the Predisposed Flatcoated Retriever Dog Display Variation in Gene Expression

Examination of gene functions in specific tumor types improves insight in tumorigenesis and helps design better treatments. Due to the rarity of histiocytic/dendritic cell sarcoma in humans, it is difficult to accrue such knowledge. Therefore, comparative research of these cancers in predisposed dog breeds, such as the Flatcoated retriever, can be of value. Histiocytic sarcoma in the dog can be grouped into a soft tissue- and visceral form. The soft tissue form at first is localized, while the visceral form progresses more quickly to a terminal state, which might be related to variations in gene expression. Microarray analyses were performed on fresh-frozen tissue from Flatcoated retrievers with either soft tissue- or visceral histiocytic sarcoma. Expression differences of ten most significantly differentially expressed genes were validated with quantitative real-time PCR (q PCR) analyses. Q PCR analyses confirmed the significantly aberrant expression of three of the selected genes: C6 was up-regulated; CLEC12A and CCL5 were down-regulated in the visceral histiocytic sarcoma compared to the soft tissue form. The findings of our study indicate that these two forms of histiocytic sarcoma in the dog display a variation in gene expression and warrant analysis of functional changes in the expression of those genes in these rare sarcomas in man.