01889-G: Innovations in Prevention, Diagnosis, and Treatment of Cancer - Goldens Lead the Way

Grant Status: Open

Grant Amount: $360,933
Dr. Jaime F Modiano, VMD PhD, University of Minnesota
January 1, 2014 - December 31, 2017
Sponsor(s): Golden Retriever Foundation, Akita Club of America, Inc., American Bullmastiff Association, American German Shepherd Dog Charitable Foundation, Inc., American Shih Tzu Club, Inc., Australian Shepherd Health & Genetics Institute, Basset Hound Club of America, Inc., Clumber Spaniel Health Foundation, English Cocker Spaniel Club of America, Flat-Coated Retriever Foundation, German Shorthaired Pointer Club of America, Inc., Gordon Setter Club of America, Inc., Irish Setter Club of America Foundation, Jeffrey Pepper, Newfoundland Club of America Charitable Trust, Portuguese Water Dog Foundation, Rottweiler Health Foundation, Saluki Health Research, Inc., Starlight Fund, United States Australian Shepherd Association, Vizsla Club of America Welfare Foundation, Yorkshire Terrier Club of America Foundation, Inc.
Breed(s): Golden Retriever
Research Program Area: Oncology - Lymphoma

Abstract

Lymphoma and hemangiosarcoma are major health problems in Golden Retrievers, causing both suffering and premature death. Through ongoing collaboration, Drs. Jaime Modiano, Matthew Breen, and Kerstin Lindblad-Toh have identified several regions of the genome that contain genetic heritable risk factors for lymphoma and hemangiosarcoma in Golden Retrievers. They have tumor-specific mutations that occur recurrently in both cancers, some of which are linked to duration of remission when treated with standard of care. Their results indicate that a few heritable genetic risk factors account for as much as 50% of the risk for these cancers. These findings offer the potential to develop tests and strategies for DNA tests that can predict risk for individual dogs, as well as to manage risk across the population as a whole. Indeed, both the inherited risk factors and tumor mutations point to pathways that have been implicated in the pathogenesis of lymphoma and hemangiosarcoma, and thus should inform the development of targeted therapies. In the current study, Drs. Modiano, Breen, and Lindblad-Toh will find the precise mutations for the heritable genetic risk factors and to validate markers (mutations) used to determine risk at the heritable loci in a larger independent population of Golden Retrievers from the United States and from Europe in order to develop robust risk prediction tools and an accompanying DNA test. Further, they will identify and characterize tumor mutations and study their relationship to the heritable risk factors, tumor pathogenetic mechanisms, and disease outcome.

Publication(s)

Borgatti, A., Koopmeiners, J. S., Sarver, A. L., Winter, A. L., Stuebner, K., Todhunter, D., … Vallera, D. A. (2017). Safe and Effective Sarcoma Therapy through Bispecific Targeting of EGFR and uPAR. Molecular Cancer Therapeutics.

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