Lymphoma strikes 1 in 8 Golden Retrievers, approximately one-third of the cases being B cell. While T cell classifications currently inform therapy choices for dogs, B cell classifications have been investigated little in Golden Retrievers. Epigenetic DNA methylation changes clearly underlie lymphomagenesis in humans, but have been evaluated minimally in dogs. Cancers con-tain tumor initiating cell (TIC) populations that resist therapy by expressing efflux pump and pro-survival genes that have not been identified clinically in lymphoma of dogs. We propose to improve diagnostic, classification, and prognostic ability using flow cytometry paired with biopsy to characterize the B cell lymphomas of Golden Retrievers. With these same samples, we will identify DNA methylation changes in lymphoma cells not present in normal cells to develop bi-omarkers of each class of lymphoma and identify new therapy targets for affected Goldens. More significantly, because DNA methylation changes occur so early in the process of cancer formation, we hypothesize that they could serve as biomarkers of risk, allowing medicine or diet to prevent lymphoma in Goldens before it develops. Finally, we propose to identify TICs in lymphoma biopsies to characterize stem-like cells by surface markers and DNA methylation changes. Identifying these cells will aid therapeutic strategy development. Each project advances a current frontier of research. By performing them in parallel, the markers from each can be combined, correlated, and translated into biomarkers of risk, diagnosis, and prognosis to advance the prevention and management of lymphoma in Golden Retrievers.
- Characterize the types of B cell lymphoma in Golden Retrievers by flow cytometry.
- Define the methylomes of B cell lymphomas in Golden Retrievers.
- Identify and characterize subpopulations of cells within types of B cell lymphoma in Golden Retrievers with TIC phenotype
Dr. Jeffery N. Bryan, DVM, PhD
University of Missouri, Columbia