Use of the Canine Genome May Help Develop Cancer Therapies

05/10/2005

Each cell of the dog contains a complete copy of the canine genome, made up of 78 biological filing cabinets - chromosomes.  The "normal" structure of these chromosomes is well documented, and when cells divide, exact copies of each chromosome are usually passed on to new cells.  However, during the development and/or progression of cancerous cells, chromosomes frequently undergo rearrangements that result in the gain or loss of genes and/or the reorganization of the genome.  A consequence of this process is a restructured genome that may affect the function of those genes – chromosome rearrangements may bring together genes that normally reside on different chromosomes.  This change can result in the generation of abnormal and/or new gene products.  In human medicine it has been shown that many tumors present with non-random chromosome aberrations, many of which are characteristic of specific types of numerous human cancers.  In addition, some of the chromosome aberrations also have been linked to response to therapy and prognosis.  Oncologists use the detection of these aberrations to assist in the determination of the most appropriate clinical management of patients.  The knowledge of such aberrations has identified areas of the human genome to be targeted for further research to develop new therapies.

One of the exciting aspects about this research is that humans and dogs have highly comparable cancers and share the same environment.  Recent sequencing of the canine genome has also shown that both species have very similar genomes.  As a consequence research being conducted is opening dialogues across research and investigative areas – research that can be readily shared across several disciplines.  

In the dog, the extent and identity of chromosome aberrations associated with specific cancers is still largely unknown.  With funding from the AKC Canine Health Foundation (CHF),  the laboratory of Dr. Matthew Breen at the North Carolina State University College of Veterinary Medicine has developed a canine cancer cytogenetics ‘toolbox’ that allows the presence of chromosome changes associated with canine cancers to be evaluated.  Using this toolbox Dr. Breen’s group, in collaboration with the laboratories of other CHF-funded investigators (Dr. Jaime Modiano and Dr. Natasha Olby), have already shown that canine cancers, including canine lymphoma, leukemia, brain tumors and osteosarcoma, present with recurrent chromosome aberrations. 

The researchers’ current work is now focused on evaluating the prognostic significance of these aberrations.  In addition, the availability of a high quality canine genome sequence has provided a key resource that allows investigators to search the genome sequences of these aberrant chromosome regions and identify candidate genes that may be playing a role in cancer development.  This research may lead to improved therapy for dogs (and eventually humans) diagnosed with cancer.

 

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