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.
