Osteosarcoma             Abstract from CHF website

Broad Institute MIT (Non-profitOrganisation)

Active Grant No: 757A:

Hereditary Mutations in Genes Associated with Osteosarcoma in Large Dog Breeds

Disease(s):  Cancer: Osteosarcoma

Sponsor(s):

    Akita Club of America, Inc., Flat-Coated Retriever Foundation, Golden Retriever Foundation, Great Pyrenees Club of America, Leonberger Health Foundation, Rottweiler Health Foundation, Saluki Health Research, Inc., Starlight Fund

Researcher(s): Kerstin Lindblad-Toh, PhD

Breed(s): Greyhound, Rottweiler

Abstract:

    Osteosarcoma (OSA), or bone cancer, affects 8,000 - 10,000 dogs in the United States annually. Large and giant breeds are at a much higher risk for this disease, suggesting that inherited risk factors are involved. Roughly 10 - 15 percent of Rottweilers, a mastiff-type breed and 15 - 20 percent of Greyhounds, a long-limbed hound-type breed, get the disease. Recently, we have identified several regions of the canine genome that are associated with an increased risk for OSA in Rottweilers. A similar study is underway for Greyhounds and is expected to identify additional regions of importantce. The purpose of this study is to identify the actual genes and mutations causing the increased risk for bone cancer in Rottweilers and Greyhounds. We will then determine the frequency of mutations in these genes in OSA in other breeds as well as in other tumors. This work should allow the development of specific genetic tests for carriers of OSA and suggest further studies leading to improved treatments for bone cancer.

March 31st 2008 Update Report for Sponsors:

0757A&B

We have identified genomic regions associated with OSA in Rottweilers and Greyhounds using genome-wide association with the newly developed ~27,000 SNP array. Results of genome-wide scans show that three regions are associated with OSA from the genome-wide screen in Rottweilers and three different and non-overlapping regions are associated with OSA in Greyhounds.  In this study, we have proposed to conduct further fine-mapping of these candidate regions using additional Rottweiler samples paired with Mastiff-type breeds (Golden Retrievers and Leonbergers) and, likewise, additional Greyhound samples paired with long-limbed hound type breeds (Irish Wolfhounds and Great Danes). We have also proposed to identify disease-associated mutations by re-sequencing candidate genes in the regions that have been narrowed by fine mapping. Finally, we will determine the frequency of these mutations in other breeds and tumor types.