2008 MCOA Cancer Sub-Committee Report

Chair: 

  Jenny Zinn-Boyce (562) 833-2291, jzinnboyce@aol.com

Members:

  Caroline Tobin – RonTobin@aol.com

  Danielle Brown – DanieBrown@aol.com

  CeCe Wardell – cecewardell@yahoo.com

The Cancer Committee would like to thank all the people who have donated blood samples from their Mastiffs over the past year.  We would especially like to thank those that have Mastiffs affected with cancer and have contributed.  We have seen the numbers of our samples increase and yet there is always a demand for more.  We are currently working on ways to consolidate these efforts so that blood and DNA is shared between researchers and the process is streamlined and more user friendly.

CURRENT RESEARCH

Mapping Hereditary Mutations in Genes Associated with Osteosarcoma in Large Breed Dogs;

The Dog Genome Sequencing Project at Broad Institute of Harvard and MIT

Chief Investigators, Dr. Kerstin Lindblad-Toh and Dr. Kenine Comstock

http://www.broad.mit.edu/mammals/dog/pdfs/dog_project_info.pdf

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.  As we know all too well, cancer especially osteosarcoma is very prevalent in our breed.  The purpose of this study is to identify the mutations causing the increased risk for bone cancer. 

The first breeds to be studied were Rottweilers and Greyhounds.  To do this, the researchers have compared the genotypes of dogs diagnosed with osteosarcoma to healthy older dogs using a statistical analysis.  They have localized genetic risk factors that are associated with OSA to three chromosomal regions in Greyhounds and Rottweilers 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 osteosarcoma.

For the next phase of this research, they have assembled a panel of samples for fine-mapping, focusing primarily on nine breeds; Mastiffs, Rottweilers, Greyhounds, Golden Retrievers, Labrador Retrievers, Leonbergers, Great Pyrenees, Great Danes and Irish Wolfhounds. 

We have submitted 207 blood samples as of March 31, 2008.  That is a definite increase from last year!!!  Thanks to all who have participated as you have made it possible to have Mastiffs included in this study!  The breakdown is as follows:

148 samples of healthy mastiffs under age 8

38 samples of healthy mastiffs over age 8 (control group – tripled from last year!!!!)

21 samples of mastiffs affected with osteosarcoma

If you have a Mastiff that has participated in the BROAD-MIT Cancer Study and the dogÕs health status has changed, please contact them and give them the updated health information.

GRANTS PARTIALLY FUNDED BY THE AKC CHF MASTIFF DONOR ADVISED FUND

Pending Grant No. 976:  Investigating the Role of STAT3 Activation in Canine Osteosarcoma

Principal Investigator(s):  Cheryl London, DVM, PhD, Ohio State University

Abstract: Osteosarcoma (OSA) is the most common bone tumor in dogs and despite aggressive treatment with amputation and chemotherapy, nearly all dogs die of their disease within 2 years of diagnosis.  Unfortunately there have been no significant advancements in the treatment of OSA over the past 15 years.  Our laboratory has been working on defining the molecular biology of OSA and has recently identified a cellular pathway that appears to be important for OSA cell survival.  This involves a protein called STAT3 that is often abnormally activated in human cancers and has not yet been investigated in canine cancers.  Several canine OSA cell lines tested were found to have excessive STAT3 activation indicating that this pathway may be useful for therapeutic intervention. In support of this, our preliminary data demonstrate that an inhibitor of STAT3 activation is capable of killing canine OSA cell lines.  The purpose of this grant is to perform a more thorough evaluation of STAT3 in canine OSA by determining the actual prevalence of STAT3 activation in canine OSA and by testing the ability of new STAT3 inhibitors developed by our collaborator at Columbus ChildrenÕs Hospital to kill OSA cell lines.  These studies will define the role of STAT3 in canine OSA and lay the groundwork for future clinical trials of STAT3 inhibitors in dogs with devastating disease.

Pending Grant No. 613:  The Prognostic Significance of Chromosome Aneuploidy in Canine Lymphoma

Principal Investigator(s):  Matthew Breen, PhD, North Carolina State University

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.

Pending Grant No. 947A&B:  Heritable and Sporadic Genetic Lesions in Canine Osteosarcoma

Principal Investigator(s):  Matthew Breen, PhD, North Carolina State University and Jaime Modiano, VMD, PhD, University of Minnesota

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.

SUMMARY

In summary, the Cancer Committee still feels that the most important thing that we can do as guardians of our beloved breed is to continue to gather blood samples and DNA from all mastiffs.  We should continue to provide Broad Institute at Harvard with samples, but even as important we should be banking the DNA at the CHIC DNA Repository and OptiGen for future research. 

GOALS

To facilitate a program that simplifies blood submission procedures that makes DNA readily accessible for several researchers to share.

To develop an outreach program to Veterinary Oncology Specialty Groups to reach mastiff owners that seek cancer care and provide research information to them.

RESOURCES

CHIC DNA Repository Information:  http://www.caninehealthinfo.org/dnabank.html

Modiano Lab: http://www.modianolab.org/studyInfo/studyInfo_osteosarcoma.shtml

Broad Institute Canine Genome Project: www.broad.mit.edu/mammals/dog

Veterinary Cancer Society: www.vetcancersociety.org

Bone Cancer Dogs: www.bonecancerdogs.org