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Rottweiler Health Foundation Mission Statementimage: Trotting Rottweiler

To raise money to fund critical research into the genetic, communicable and acquired diseases that plague our beloved breed, the Rottweiler.

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Summer 2008

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GRANTS BEING FUNDED


Grants Currently Being Funded by the Rottweiler Health Foundation
  • Five-year grant to Dr. Waters and his team to continue their pursuit of the important factors that regulate cancer resistance and exceptional longevity in our Rottweilers and humans. (June, 2007)

Grants Currently Being Funded by the Rottweiler Health Foundation (with *AKC/CHF Matching Funds)

March, 2008 - RHF commits $50,000 over the next three years to CHF Grant Numbers 757A/B, 947A/B, 613, and renews funding for 778.

GRANT 757 A/B
Hereditary Mutations in Genes Associated
with Osteosarcoma in Large Dog Breeds

Kerstin Lindblad-Toh, PhD, Broad Institute
Kenine Comstock, PhD, University of Michigan Medical School

Participating breed clubs

Research supported by the Rottweiler Health Foundation, the Leonberger Health Foundation, and Saluki Health Research, Inc.
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 importance.  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.

 

GRANT 947A/B
Heritable and Sporadic Genetic Lesions in
Canine Osteosarcoma

Matthew Breen, PhD, North Carolina State University
Jaime Modiano, VMD, PhD, University of Minnesota

Participating breed clubs

Research supported by the Rottweiler Health Foundation, the Leonberger Health Foundation, and Saluki Health Research, Inc.

Abstract

Certain dog breeds are prone to develop certain types of cancer. Yet, there has been little progress to define the genes that account for this risk. For this project, we will use contemporary technologies to identify genetic abnormalities that are shared by bone tumors and segregate with risk in two dog breeds (Rottweilers and Golden Retrievers) where the disease is prevalent. In collaboration with our colleagues at the University of Michigan and the Broad Institute, we have identified preliminary regions of the genome that may influence risk in Rottweilers. The work described here represents a next step to pinpoint specific genes that are associated with breed-dependent risk, and to predict how heritable factors influence bone cancer in Rottweilers, Golden Retrievers, and other dogs.

 

GRANT 613
The Prognostic Significance of Chromosome Aneuploidy
in Canine Lymphoma

Matthew Breen, PhD, North Carolina State University

Participating breed clubs

Research supported by the Rottweiler Health Foundation.
Abstract

Canine lymphoma accounts for almost a quarter of all cancers in the dog.  Despite improvements in veterinary medicine, the response to treatment for canine lymphoma continues to be highly variable with no reliable means to predict response. In human lymphoma the presence of characteristic chromosome aberrations has been shown to have both diagnostic and prognostic significance. With previous funding from the AKC CHF we have identified a series of recurrent chromosome aberrations in canine lymphoma, some of which also correlate with different sub-types of lymphoma.  In this project we will test for the presence of these chromosome aberrations in over 300 cases of canine lymphoma derived from dogs that were all treated with the same chemotherapy protocol as part of a clinical trial.  This approach will allow us to determine if these frequent chromosome aberrations correlate with the duration of disease free interval in the study population and thus are of prognostic significance. This project therefore offers real potential to increase the sophistication of diagnosis and prognosis for canine lymphoma and thus provide a means to improve the health and welfare of dogs diagnosed with lymphoma.

 

GRANT 768
A Collaborative Study by Veterinary Oncologists, Pathologists and Diagnostic Laboratories to Enhance the Detection, Diagnosis and Treatment of Canine Lymphoma
Ted Valli, DVM, University of Illinois

Participating breed clubs

Research supported by American Bullmastiff Association, Briard Club of America, Scottish Terrier Club of America Health Trust Fund, John Hoffman Fund for Miniature Schnauzer Research, Starlight Fund, Golden Retriever Foundation, Flat-Coated Retriever Foundation, Dr. William R. Newman, Bernese Mountain Dog Club of America, German Wirehaired Pointer Club of America, Portuguese Water Dog Foundation, Rottweiler Health Foundation, and Orthopedic Foundation for Animals.
Background

Lymphoma is the most common canine cancer treated by chemotherapy and a most common neoplasm that afflicts dogs of all breeds and ages. The completion of the canine genome has shown the remarkable similarities to that of humans. Similarly, many of the malignancies that occur in dogs are also like their human counterparts especially for the tumors of the lymphoid system. The World Health Organization has devised a new system of recognizing and categorizing the many subtypes of lymphoid tumors with very different characteristics that must be considered in providing effective treatments. Currently lymphomas in dogs are treated as if they are all of the same type, but we now find that like those in humans the canine lymphomas are of many types that also benefit from specific identification and treatment. The goal of this study is to demonstrate that veterinary diagnosticians can effectively apply the human criteria to the canine tumors and thus permit much more effective treatment by veterinary oncologists.  This application will alter costs of treatment according to tumor type and increase survival in animal companions that share our lives and environments.

GRANT 778
Role of Regulatory T Cells in Dogs with Osteosarcoma
Barbara Biller, DVM, Colorado State University

Participating breed clubs

John Hoffman Fund for Miniature Schnauzer Research, American Bullmastiff Association, Starlight Fund, Flat-Coated Retriever Foundation, Golden Retriever Foundation, Rottweiler Health Foundation, the Orthopedic Foundation for Animals.

Abstract

Regulatory T cells (Treg) are type of lymphocyte that prevent the immune system from attacking self tissues.  Human cancer patients, however, frequently have abnormally high numbers of Treg which can directly interfere with the immune system’s efforts to detect and kill cancerous cells.  Whether dogs with cancer have increased numbers of Treg is currently unknown.  We have developed a method to identify canine Treg and will use this tool to determine whether dogs with a particular type of bone cancer (osteosarcoma) have increased levels of Treg compared to healthy dogs.  We will also investigate whether surgical removal of the tumor and the type of chemotherapy given after surgery increases or decreases Treg numbers.  By studying how different treatments for osteosarcoma affect Treg we may be better able to identify chemotherapy drugs that deplete Treg and ultimately improve anticancer therapy for dogs with osteosarcoma and other types of cancer.

Progress View progress reports (Fall, 2007)

GRANT 790
MicroRNA Profiling and MicroRNA-Based
Treatment of Canine Cancers

William Kisseberth, DVM, Ohio State University

Participating breed clubs

American Bullmastiff Association, Scottish Terrier Club of America Health Trust Fund, Starlight Fund, Golden Retriever Foundation, Flat-Coated Retriever Foundation, John Hoffman Fund for Miniature Schnauzer Research, Tualatin Kennel Club, Bernese Mountain Dog Club of America, Portuguese Water Dog Foundation, Rottweiler Health Foundation, and Orthopedic Foundation for Animals.

Background

Cancer is a common disease in dogs of all breeds and is a leading cause of death. Because cancer is fundamentally a genetic disease, both understanding the genetic basis of cancer and treating cancer are relevant to dog owners and breeders alike. Much of the progress in diagnosis, prognosis, and treatment of cancer in people has been the result of advances in “genomics”. Recently, the canine genome has been sequenced, providing the opportunity to apply new genomic approaches to better understand and treat cancer in the dog. MicroRNAs (miRNA) are small non-protein coding molecules that have been implicated in humans as having an important role in cancer and a variety of other diseases. In this study, we will identify miRNAs in selected common canine cancers (osteosarcoma, transitional cell carcinoma, melanoma) using miRNA microarrays. We will then identify miRNAs that are potential targets for new cancer therapy drug development. MiRNAs that significantly effect cancer cell growth will be investigated further to determine how they exert their effects. The goals of this study are to identify important canine miRNAs that can be used to improve cancer diagnosis and treatment in the dog.

GRANT 705A
Characterization of Fluorine-18-Fluorodeoxyglucose Uptake in Dogs with Cutaneous Mast Cell Tumor and Malignant Lymphoma
Amy LeBlanc, DVM, DACVIM, University of Tennessee

Participating breed clubs

Research supported by the Akita Club of America, Inc., American Boxer Charitable Foundation, American German Shepherd Dog Charitable Foundation, Bernese Mountain Dog Club of America, Briard Club of America, Chinese Shar-Pei Charitable Trust, French Bulldog Club of America, Golden Retriever Foundation, Labrador Retriever Club, Newfoundland Club of America Charitable Trust, Portuguese Water Dog Club of America, Inc., Rottweiler Health Foundation, St. Bernard Club of America
Background The University of Tennessee's College of Veterinary Medicine (UTCVM) has a unique opportunity for collaboration with the Cancer Imaging and Tracer Development Research Program (CITDRP) at the University of Tennessee Medical Center. The UTCVM has established a strong collaboration with the CITDRP for the benefit of human and veterinary patients. We will use PET imaging to study cutaneous mast cell tumor (MCT) and canine lymphoma (LSA) in dogs.  Whole-body PET scanning is uniquely suited for staging with evaluation of the skin, lymph nodes, spleen and liver for early signs of metastatic spread.  All of these sites can be imaged in one non-invasive procedure, using uptake of the 18F-labeled glucose analog 2-deoxy-D-glucose (18FDG), to identify sites of metastasis.

The proposed pilot study will evaluate the uptake of 18FDG in 30 tumor-bearing dogs (15 with MCT, 15 with LSA) using PET.  All dogs will have their cancer diagnosed and staged using standard imaging techniques and results will be compared with whole-body PET results.

GRANT 632
MicroRNAs and Canine Lymphoma
Dr. Kisseberth; Ohio State University (2 years)

Participating breed clubs

Research supported by the Rottweiler Health Foundation and the Canine Health Foundation.
Background Lymphoma is one of the most common cancers in the dog. Current methods of classifying lymphoma neither explain nor predict its variable clinical behavior. Much of the progress in diagnosis, prognosis, and treatment of lymphoma and other cancers in people has been the result of advances in "genomics." Recently the canine genome has been sequenced, providing the opportunity to apply new genomic approaches to better understand and treat cancer in the dog. MicroRNAs (miRNA) are small non-protein coding molecules that have been implicated in humans as having an important role in cancer and a variety of other diseases. In this study, we will identify miRNAs using bioinformatic methods. We will then use miRNA microarrays to analyze normal canine tissues and canine lymphoma biopsies. These results (miRNA expression profiles) will be correlated with histologic diagnosis and clinical parameters.

The goals of this study are to identify canine miRNAs and their normal patterns of expression and to determine if specific histologic subtypes of lymphoma are characterized by unique miRNA expression profiles, if specific miRNAs have prognostic significance, and to identify potential targets for future investigation and therapies. This study will also generate new tools for future miRNA investigation in the dog.

Progress View progress reports (Fall, 2007)

GRANT 615
Heritable and Sporadic Genetic Lesions in Canine Lymphoma
Dr. Breen, North Carolina State University and
Dr. Jaime Modiano, University of Colorado (2 years)

Participating breed clubs

Research supported by the Rottweiler Health Foundation and the Canine Health Foundation.
Background It has been apparent for some time that certain dog breeds are prone to develop certain types of cancer.  Specifically, studies completed between the late 1960's and the early 1980's defined relative risk of lymphoma for different dog breeds.  Yet, there was little progress since then to define factors that account for this risk. As part of ongoing programs supported by the AKC CHF in our laboratories, we showed recently that the breed-specific risk of lymphoma extends beyond the simple disease condition to a predisposition for specific forms of lymphoma. More importantly, we showed there are recurrent chromosomal abnormalities that segregate with specific forms of lymphoma and that are more common in Golden Retrievers (with that form of the disease) than in other breeds, suggesting breed-specific profiles of genetic abnormalities will be found in canine lymphoma. 

To continue this work, we plan to use contemporary "array-based" technologies to identify genes that map to these regions and how they contribute to the disease. We anticipate that the results from this work will allow us to predict how heritable factors influence the occurrence of abnormalities in these genes, and will set the groundwork to identify specific genes associated with breed-dependent cancer risk.

GRANT 247
The Study of the Genetics of Cranial Cruciate Ligament Disease in the Dog
Max Rothschild, Ph.D.

Participating breed clubs

Research supported by the Newfoundland Club of America Charitable Trust, Rottweiler Health Foundation
Background Cranial cruciate ligament disease (CCLD) is the cause of limping in nearly 20 percent of all dogs that are taken by their owners to veterinarians for lameness. CCLD causes instability in the knee, swelling and pain. Surgery to stabilize a torn CCL costs individual dog owners thousands of dollars and the dog owning public tens of millions of dollars each year and even with surgery, debilitating arthritis occurs and progresses. CCLD commonly occurs in particular breeds of dogs (e.g. Labrador Retreiver, Rottweiler, and Newfoundland) while other breeds (e.g. Greyhound, German Shepherd) rarely develop this problem. When a disease is seen with increased frequency in particular breeds of dogs, this supports the probability that a disease, in this case CCLD, is hereditary.

Using this information we have already collected pedigrees and genetic material (DNA) from normal and CCLD affected Newfoundlands. The pedigrees will be used to determine a pattern of inheritance (i.e. simple recessive, sex-linked) for CCLD. The DNA will be used to search for genetic markers that differ between normal and affected dogs and may serve as disease predictors. These markers will then allow identification of carriers of CCLD, and potentially reduction or elimination of CCLD from the dog population.

GRANT 373A
Mapping Genes Associated with Osteosarcoma in Large Dog Breeds
Kenine E Comstock, Ph.D., University of Michigan, 
Kerstin Lindblad-Toh, PhD., Broad Institute
Dr. Jaime Modiano, University of Colorado

Participating breed clubs

Research supported by the Borzoi Club of America, Forsyth Kennel Club, Golden Retriever Foundation, Great Pyrenees Club of America, Great Pyrenees Club of Puget Sound, Greyhound Club of America, Irish Setter Club of America Foundation, Irish Wolfhound Club of America, Inc., Newfoundland Club of America Charitable Trust, Rhodesian Ridgeback Club of the United States, Rottweiler Health Foundation, St. Bernard Club of America, Starlight Fund

Background Eight thousand to ten thousand cases of osteosarcoma, a malignant bone tumor, are reported in dogs in the United States annually, representing a significant health concern. In the majority of cases, spread of the tumor throughout the body and death follows within a few years.  Osteosarcoma affects all dogs, but the disease frequency is considerably higher in large and giant breeds, including the long-limbed hounds (Irish Wolfhound, Great Dane, Greyhound, Scottish Deerhound, Rhodesian Ridgeback, Great Pyrenees and Borzoi) and Mastiff-type breeds (Rottweiler, Labrador Retriever, Flat-Coated Retriever, Golden Retriever, Mastiff, Bullmastiff, Saint Bernard, Irish Setter, and Newfoundland).

Osteosarcoma, or bone cancer, is a significant health concern in large dog breeds affecting roughly 10-15% of Rottweilers.  Amputation and chemotherapy are the preferred treatment, but the survival rate is only 20% after two years due to frequent metastasis.  Determining the genetic risk factors for the disease would make it possible to develop genetic tests for carriers of osteosarcoma in Rottweilers and possibly other related breeds. It would also allow for better understanding of the disease which could enhance treatment both in dogs and in people with bone cancer.

It is clear the genetics play an important role. We propose to identify the genetic risk factors for osteosarcoma in two breeds: Greyhound and Rottweiler. While certain characteristics of these two breeds make them ideal to study, we expect that the genes identified in these breeds may also be associated with osteosarcoma in related breeds. This study should lead to the development of genetic tests for osteosarcoma that could be used to eliminate carriers from breeding populations, eventually reducing the frequency of this devastating cancer. Ultimately, it could also lead to improvements in treatment of osteosarcoma.  Our breed was chosen to participate in this study because of the excellent response made in other cancer studies and because the disease is so prevalent.  We aim to identify osteosarcoma risk factors in Rottweilers taking advantage of the tools developed in conjunction with the dog genome sequencing project.

STUDY IN PROGRESS   Collection of blood samples from 100-200 Rottweilers affected with osteosarcoma and 100-200 healthy dogs that are 8 years or older are needed.  Using genomic DNA from these samples we will search the genome for regions that are different in affected and healthy dogs. This will lead us to the defective gene causing the cancer and will permit us to design carrier tests and ultimately to design better treatment.

GRANT 415
Anti-HLA-DR Antibody Therapy in Canine B-cell Lymphoma
Preliminary Clinical Evaluation

Rodney Page, MS, DVM, Cornell University

Participating breed clubs

Research supported by the Rottweiler Health Foundation and the Canine Health Foundation.

Background

The goal of this research is to use a therapy which has proved effective in human non-Hodgkin’s lymphoma. This therapy uses an antibody which recognizes cancer cells and kills them. This antibody has been confirmed safe in dogs.

The proposal is to optimize the administration of this antibody in dogs who have already failed chemotherapy. The safety and potential efficacy will be evaluated. 

GRANT 0305
Histocompatibility Alleles Conferring Susceptibility to Canine Diabetes, Immune-Mediated Thyroiditis and Immune-Mediated Hemolytic Anemia
Dr. Wayne Potts, University of Utah

Participating breed clubs

Research supported by the Rottweiler Health Foundation and the Canine Health Foundation.

Background

Research into autoimmune diseases in humans has shown that a specific gene must exist for a specific autoimmune disease to develop.

Dr. Potts proposes to collect DNA samples from purebred dogs who have Canine Diabetes, Immune-Mediated Thyroiditis and Immune-Mediated Hemolytic Anemia. He will collect from 100 different purebred dogs who have each of these three diseases. 

After cloning and sequencing, the DNA will be tested for significant associations with each of the autoimmune diseases.

COMPLETED
GRANT 2620

Determination of the Clinical Phenotype and Inherited Nature of Familial Subvalvular Aortic Stenosis in the Rottweiler
Dr. Kathryn Meurs, DVM, PhD, DACVIM

Participating breed clubs

Research supported by the Rottweiler Health Foundation, the Medallion Rottweiler Club and the Canine Health Foundation.

Background

Subvalvular Aortic Stenosis (SAS) is a congenital heart disease characterized by a fibrous ridge located below the aortic valve.  Affected dogs are at risk of developing heart valve infections, congestive heart failure or sudden death SAS defects have been shown to be inherited in the Newfoundland breed, and is likely to be inherited in the Golden Retriever, Boxer and Rottweiler, among others.  Since this is a familial defect in at least some breeds, affected dogs should not be bred.

The first step in the research project is to characterize heart disease (SAS) in the Rottweiler.  SAS is a very different disease between breeds.  It is therefore difficult to extrapolate data found in the Boxer or the Golden to the Rottweiler.  The objectives of the study are to define the clinical (phenotypic) and genotypic characteristics of SAS in the Rottweiler.  A genome wide scan will be performed to identify informative canine markers associated with SAS. 

STUDY COMPLETE

Read findings/results; read more on SAS

COMPLETED
GRANT
Incidence and Breed Related Risk Factors
for Gastric Dilation-Volvulus in Dogs
5-year prospective study by Larry Glickman, VMD, Ph.D., Purdue University

Participating breed clubs Akita, Bloodhound, Collie, Great Dane, Irish Setter, Irish Wolfhound, Newfoundland, Rottweiler, Saint Bernard, Standard Poodle, Weimaraner and the AKC/CHF.
Method

Investigator measured dogs at dog shows and the owners completed a detailed questionnaire concerning the dogs medical history, genetic background, husbandry and eating practices, personality and diet.

Five years later, the investigator called and conducted a follow-up on each the dog.

The incidence of bloat (GDV) was calculated for each breed.

Risk factors were compared to dog measurements and questionnaire responses to determine any correlation.

STUDY COMPLETE

Results for the Rottweiler

(Data based on 200 dogs)
  • Of the 11 breeds tested, the Rottweiler had the lowest incidence of Bloat (1%).

  • "Happy/easy going" dogs were found to be less prone to bloat. Rottweiler was listed as the easiest going/confident dog of the 11 breeds surveyed.

  • Overweight dogs were less prone to bloat.

  • Dogs that are feed 2 - 3 times a day are less prone to bloat.

  • Restricting water before or after eating, or elevating the dogs food bowl increased the incidence of bloat.

  • Bloat incidence was found to increase with age.

  • Giving dogs anti-gas medication on a regular basis, increased the incidence of bloat by 66%.

  • Do not breed any animal if there has been a 10 relative that has previously bloated.

GRANT
Causative Mutation for von Willebrand’s Disease
George J. Brewer, MD University of Michigan Medical School

Participating breed clubs American Miniature Schnauzer Club, American Rottweiler Club and Poodle Club of America. A previous study was completed with Dobermans, Scottish Terrier, Manchester Terrier, Pembroke Welsh Corgis and the AKC/CHF
Background

Von Willebrand’s disease is a bleeding disorder, common in humans and dogs. The gene has been cloned in human and many different mutations have been found.

In Brewer’s original study, three mutations were found in the canine gene.

Type III (severe) vWD in Shelties and the Scottie is an autosomal recessive that completely knocks out the function of the gene.

Type I (mild) - vWD was found in Dobermans, Manchester Terrier, Poodles and Pembroke Welsh Corgis. The mutation is due to a different autosomal recessive splice site mutation that knocks out 90% of the gene function. The remaining 10% normal functioning gene results in a milder disease.

STUDY IN PROGRESS
Partial Results

The frequency of the mutation is very high in Dobermans:

  • only 20% of the breed is clear of a genetic mutation for vWD

  • 30 % of the breed is affective

  • 50 % of the breed are carriers of the genetic mutation.

Genetic testing is now available to identify affected dogs and remove them from breeding programs.

Breeding clear to clear dogs or careful breeding of clear to carrier dogs will gradually eliminate the problem in two to three generations.

Brewer has not been able to identify the mutation in the Rottweiler yet. It is most likely a different mutation than other breeds previously studied.

This project is currently on going.


GRANT
Identifying the Genetic Cause of Canine Hip Dysplasia
George J. Brewer, MD University of Michigan Medical School

Participating breed clubs Research supported by the Alaskan Malamute Club of America, American Rottweiler Health Foundation, Samoyed Club of America Research and Education Foundation and the AKC/CHF.
Background

Canine hip dysplasia is the number one genetic health problem in dogs, with a frequency in over 100 breeds.

The mode of inheritance may be polygenic (due to more than one gene). However, with the proper approach, a polygenic disease can be solved.

The goal of the project is to develop a DNA test to identify affected and carrier animals, to eliminate the disease through selective breedings.

STUDY IN PROGRESS
This study is on-going. Brewer is currently collecting blood samples to perform a genome wide scan to identify the genes associated with this crippling disease.

COMPLETED
GRANT1626T
Canine Cancer - Significance of Tumor Suppressor Genes
Jaime Modiano, VMD, Ph.D., AMC Cancer Center, Denver, CO

Participating breed clubs American Boxer Charitable Foundation, Golden Retriever Foundation, Great Dane Club of America, Medallion Rottweiler Club, Rottweiler Health Foundation, Scottish Terrier Club of America Health Trust Fund
Background

Lymphomas and leukemia (cancer of the white blood cells), melanomas (tumors of pigmented cells responsible for skin coloring) and Osteosarcoma (cancer of the bone) are among the most common cancers in dogs. Osteosarcoma occurs commonly in Rottweiler and many other giant breeds.

Clustering of specific cancers in a breed and families suggests a hereditary component may be important in the development and progression of the disease.

Cancer is a term that refers to a large number of diseases whose only common feature is uncontrolled cell growth and proliferation. Cancer can affect any dog of any breed at any age.

Normally, tumor suppressor genes would constrain renegade cells, but mutations can disable these genes in cancer cells, contributing to the development and progression of the cancer.

STUDY COMPLETE

Also see study info:
'Dogs, Genes, and Cancer'

The research conducted in this study will provide the basis for future research that may, ultimately, lead to scientists being able to provide a better assessment of individual's risks for cancer (or for cancer in progeny), as well as determine whether a given dog is a good candidate for a given therapy. This project has helped to broaden the understanding of why tumors happen, so that the abnormalities can be targeted and better therapies devised. Researchers developed and tested gene therapy for melanoma. In a clinical trial involving five dogs with facial or oral melanoma, they found that the gene therapy, in which tumors were injected with modified genes, was both free of adverse effects and effective. The goal of this study is to determine the frequency of mutations in tumor suppressor genes in melanoma, lymphoma and osteosarcoma.

This data will enable us to determine the relationship of tumor suppressor gene mutations with the prevalence of these cancers in high-risk breeds, as well as with prognosis and outcome.

Results from this study will hopefully give us tools to predict the risk of a particular dog or it’s off-spring to develop these devastating tumors.  The future might include molecular therapies for treating canine cancers.


GRANT
Growth Signaling Pathways in the Pathogenesis
and Treatment of Canine Cancer

Stuart Helfand, DVM, University of Wisconsin

Participating breed clubs Rottweiler Health Foundation, German Shepherd Dog Club of America, Skye Terrier Club of America, Golden Retriever Club and the AKC/CHF.
Background

Hemangiosarcoma is a common cancer in dogs that originates from cells lining the blood vessels. The spleen is a common target organ for these tumors. It can affect any dog but is seen more often in German Shepherds, Skye Terriers, Golden Retriever and to some extent in Rottweilers, suggesting this disease has an hereditary component. These tumors arise when cells respond inappropriately to growth factors, allowing the cells to divide in an uncontrolled fashion.

Tumor suppressor genes constrain or eliminate these rapidly dividing cells, but mutations in these genes can disable their ability to function properly.

STUDY IN PROGRESS

The focus of this project is to study and examine the hypothesis that the loss of function of a particular tumor suppressor genes (PTEN) leads to the increase production of tumor growth factors (VEGF).

The goal of this research project is to develop a genetic test for screening dogs for mutations i