AKCCHF grant #00615B (closed)

Jaime F Modiano, VMD PhD, [\$2500 from AKCCHF Donor Advised fund]

This is an AKCCHF Success Story! Sniffing Out Lymphoma Genes

Project Summary from AKCCHF.org website:

“We showed recently that the breed-specific risk of lymphoma extends beyond the simple disease condition to a predisposition for specific forms of lymphoma. More importantly, we showed there are recurrent chromosomal abnormalities that segregate with specific forms of lymphoma and that are more common in Golden Retrievers (with that form of the disease) than in other breeds, suggesting breed-specific profiles of genetic abnormalities exist in canine lymphoma.

To continue this work, we have used contemporary “array-based” technologies to identify genes that map to these regions and how they contribute to the disease. The results from these analysis are in many ways comforting, as they show differences that are proportional to what would be expected based on the known biology of lymphoma. In other words, tumors differ more based on phenotype (B-cell vs. T-cell) than they do based on histologic grade. Also, T-cell malignancies harbor more differences among them than B-cell malignancies. The data show that breed specific changes extend to age of onset for lymphoma, providing additional support for the central hypothesis, and we have identified preliminary regions in two chromosomes where gene expression signatures follow the same pattern of segregation for the gains and losses of DNA we identified previously. Nevertheless, gene expression differences are subtle, and in the case of breed and gender, they are few in number. This is a remarkable result, since these small differences may define genes and pathways that are heavily involved in risk and progression of the disease in specific breeds. We predict that the results from this work will allow us to define how heritable factors influence the phenotype and biological behavior of these tumors, setting the groundwork to develop better strategies for diagnosis, control, and treatment.”

Publication:

Thomas R et al.  Refining tumor-associated aneuploidy through “genomic recoding” of recurrent DNA copy number aberrations in 150 canine non-Hodgkin lymphomas.  2011.  Leukemia & Lymphoma 52:  1321-1335.