The Cytogenomic Landscape of Canine Cancer 

Speaker: Matthew Breen, PhD C.Biol FSB, North Carolina State University, College of Veterinary Medicine

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The Cytogenomic Landscape of Canine Cancer  

“Cytogenetics” is the study of inheritance in relation to the structure and function of the chromosomes. The Genome is Nature’s biological filing cabinet. It is divided into segments called chromosomes. The chromosomes are present in pairs, and composed of smaller units called DNA. Chromosomes can be banded which allows for accurate identification. DNA is the language of life; it contains specific instructions to the cells of a living organism to manufacture the proteins necessary for healthy and functional tissues. “Cytogenomics” is the study of cytogenetics using genomics approaches. Brief Guide to Genomics.

Nature’s biological filing cabinets become rearranged during cancers. In cancer, some genes are missing, some genes are duplicated, and in certain cases some genes move to new locations where they do not interact well with their new neighbors. 

It is estimated that almost 50% of all dogs over the age of 10 years will develop cancer and approximately 1 in 4 of all dogs will develop a cancer at some stage in their life.

Chromosome aberrations [abnormalities in the structure of the genetic DNA] are the hallmarks of gene deregulation and genome instability. They have been collated from assessment of more than 62,000 human neoplasms [tumors], collectively representing approximately 75 different types of cancer. There is broad acceptance that the accurate identification of recurring chromosome abnormalities in malignant cells provides opportunities to increase the sophistication of diagnosis, subclassification and prognosis of neoplastic disorders. In human medicine, the identity of cytogenetic aberrations has been shown to also assist in the localization of cancer-associated genes and even selection of the most appropriate therapeutic approach. The application of molecular cytogenetics [study of the chromosomes and how they function inside of the cell] to the analysis of human neoplasms has revolutionized the way in which we interrogate tumor cells for cytogenetic changes, whether they are numerical or structural in nature.  

Veterinary medicine has provided a wealth of information about the clinical and pathological presentation of numerous cancers in animals, and while both dogs and cats are now the subject of intense molecular cytogenetic attention, it is the dog that has provided much of the insight to date. Despite millions of years of divergent evolution, the high degree of similarity between human and dog also extends to their genome sequences. Using and comparing the data from dogs and humans allows for identification of common features that may be used to make advances in health for both. It is well known that purebred dog breeds are associated with differing susceptibility to specific malignancies, suggesting that selected breeds of dog are inheriting ‘at risk’ alleles for very few genes, perhaps even a single gene, with a profound effect. These features, combined with the sophisticated genomic resources now available for the dog, have placed the dog in a position of high visibility as a model system for cancer research. 

As pets, our dogs (and thus their genomes) are exposed to the same environmental influences as ourselves. The combination of pathophysiological and genetic similarities shared between human and dog led to our hypothesis that canine tumors would contain the natural variety of chromosome aberrations that are observed in the corresponding human cancers, a feature not evident with induced tumors in rodents. We have shown our hypothesis to be valid, by demonstrating that there are considerable cytogenomic changes shared by numerous forms of cancer that affect both human and dog. We are investigating cytogenomic changes evident in a variety of the leading cancers in dogs, including lymphoma, leukemia, osteosarcoma, histiocytic neoplasia, urogenital carcinoma, intracranial malignancies, hemangiosarcoma and melanoma. Of broader significance our data also reveal that several of the changes conserved between human and dog also extend to other animals with similar cancers. We are now aligning cytogenomic data from comparable cancers in multiple species to identify the genes likely to be of greatest significance to the malignant process. Identification of these genes is key to developing new ways to halt the cancer process and extend both the duration and quality of life of patients.  

As is the case in human cancers, detailed cytogenomic investigations of canine tumors are now revealing the identity of recurrent changes that are of diagnostic significance. The ability to characterize response-associated cytogenomic changes also now provides us with exciting opportunities to develop new prognostic assays that may be used as valuable aides in the clinical management of individual patients.

The Breen Lab at NCSU

The Breen Lab is recruiting patients for the following canine cancer studies: Lymphoma, Osteosarcoma, Hemangiosarcoma, Melanoma, Mast Cell Tumor, Bladder cancer, Prostate cancer.  For study information, send an email to [email protected].

Learn More about Cytogenetics

In 2002, Dr. Breen relocated his laboratory to NCSU’s College of Veterinary Medicine as part of its Genomics initiative. Since then his research interests have continued to focus on the genomics, genome mapping and the comparative aspects of canine cancer. Dr. Breen was a charter member, and now serves on the Board of Directors, of the Canine Comparative Oncology and Genomics Consortium (CCOGC), a 501(c) (3) not-for-profit organization established to promote the role of the dog in comparative biomedical research.

Current projects in the lab include genomic investigations of a variety of canine cancers (lymphoma, leukemia, osteosarcoma, urogenital carcinoma, intracranial cancers, melanoma, hemangiosarcoma). They are simultaneously engaged in collaborations with leading human academic medical centers to explore the translation of our findings in dogs to comparable cancers in humans.



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