CHF grant updates
According to the results from Saluki Health Surveys, hemangiosarcoma and mammary cancers are the most commonly occurring cancers in Salukis, with the next highest incidence being Lymphoma and then Osteosarcoma. To further investigations of the cancers prevalent in our Salukis, the following American Kennel Club - Canine Health Foundation Grants have been financially supported by Saluki Health Research, Inc. The progress reports from the principal investigators were received in March, 2009.
Grant No. 757A. Hereditary Mutations in Genes Associated with Osteosarcoma in Large Dog Breeds, Dr. Kerstin Lindblad-Toh, PhD, Broad Institute of MIT and Harvard, 4/1/2007-9/30/2009. 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. The purpose of this study is to identify the mutations causing the increased risk for bone cancer in Rottweilers and Greyhounds. To do this, we have proposed to compare the genotypes of dogs diagnosed with OSA to healthy older dogs using a statistical analysis. To date, we have collected ~500 blood samples from dogs diagnosed with OSA and ~1500 healthy dogs over 8 years old. Of these, we have collected 171 blood samples from Greyhounds diagnosed with OSA and 276 healthy Greyhounds over 8 years old. We have localized genetic risk factors that are associated with OSA to three chromosomal regions in Greyhounds and are currently narrowing in on the precise mutations that cause the disease. The biological effects of the mutations will be studied to better understand the cause and progression of the disease. This work should allow the development of specific genetic tests for carriers of OSA and suggest improved treatments for OSA.
Grant No. 947A. Heritable and Sporadic Genetic Lesions in Canine Osteosarcoma, Dr. Matthew Breen, PhD, North Carolina State University, 8/1/2008-7/31/2009. Osteosarcoma (OSA), bone cancer, is the most common primary malignant bone tumor, occurring spontaneously in both humans and dogs. In humans, around 900-1000 cases of OSA are diagnosed per year while in dogs more than 8000 cases are reported per year making the disease incidence in dogs nine times the incidence in humans. Previous research focusing on human and dog OSA have discovered that these tumors contain a high degree of genetic abnormalities. Several studies on human OSA have indicated that some genetic abnormalities in humans are correlated with a poor prognosis. Currently, only a little is known about how genes influence the risk and progression of bone cancer in dogs. In order to assess the degree of genetic abnormalities in dogs, we are looking genome wide for genomic changes associated with canine OSA. CHF947A has been active for just six months and during this tumor we have profiled tumor DNA from 75 dog OSA patients and have identified genetic abnormalities recurrently associated with dog OSA. In addition, using larger sample number of three breeds, Greyhounds, Rottweilers, and Golden Retrievers, we have identified genomic abnormalities that appear to be associated more frequently with one breed. Over the coming six months we will complete our genomic analysis of 100 canine OSA cases, reevaluate our data and then perform higher resolution analysis to further refine the data and define key genes of significance.
Grant 613. The Prognostic Significance of Chromosome Aneuploidy in Canine Lymphoma, Dr Matthew Breen, PhD, North Carolina State University, 8/1/2008-7/31/2010. During the first six months of this two year projects, we have shown that pooling DNA from overlapping BAC clones results in a more robust fluorescent signal than using a single BAC clone and provides a higher signal to noise ratio. We have generated the DNA used for the probes being used for this project en masse. Cells have been isolated from 120 of our 315 archival patient samples and prepared for multicolour FISH analysis. Thus far we have performed FISH analysis of the first 100 archival cases and have acquired images for each these cases. Data for the copy number of each of the four loci are being assessed and statistical evaluation indicates that at least one of the four loci may be associated with disease free interval. Over the next six months we will continue processing cases, aiming to reach 200 cases by July 2009. At the midpoint of year 1 we are ahead of our anticipated schedule.