Discovery of Biomarkers to Detect Lymphoma Risk, Classify For Treatment, and Predict Outcome in Goldens
Lymphoma is a predominant cancer affecting Portuguese Water Dogs as well as numerous other breeds of dogs. Epigenetics is one growing area of research into the behavior of cancer in both medicine and veterinary medicine.
One significant area of epigenetic research involves the investigation of changes to the genome that do not involve a change in the nucleotide sequence. Examples of mechanisms that produce such changes are DNA methylation and histone modification, each of which alters how genes are expressed without altering the underlying DNA sequence. These are important areas of human oncology research that have not been as extensively investigated in veterinary medicine.
This study has the goal of identifying epigenetic markers of lymphoma that can be used to identify dogs at risk, assist with early diagnosis, and aid in the development of individualized treatment plans for affected dogs that can eventually applied to any breed.
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.
Co-sponsored with the AKC Canine Health Foundation, Grant Number: 1918-G
Dr. Jeffery N. Bryan, DVM
University of Missouri, Columbia