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. Dr. Jeffrey Bryan, in collaboration with Drs. Anne Avery and Heather Wilson will focus their efforts on an area of emerging importance in cancer: epigenetics. Epigenetics is defined as stable and heritable patterns of gene expression that do not entail any alterations to the original DNA sequence. Epigenetic DNA methylation changes clearly underlie development of lymphoma in humans, but have been evaluated minimally in dogs. Dr. Bryan and collaborators propose to improve diagnostic, classification, and prognostic ability using flow cytometry paired with biopsy to characterize the B-cell lymphomas of Golden Retrievers. They will identify DNA methylation changes in lymphoma cells not present in normal cells to develop biomarkers 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, they hypothesize that they could serve as biomarkers of risk, allowing medicine or diet to prevent lymphoma in Goldens before it develops. Finally, they propose to identify tumor initiating cells (TIC) 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.