The genome of a dog is comprised of 78 chromosomes. These chromosomes are nature’s filing cabinets and contain all the genes (‘files’) that are required to inform cells what to do and how to behave. Many genes are associated with the regulation of cell growth, division and even death. Cancer is a term that describes a multitude of conditions with an enormous range of clinical outcomes.

One key aspect of cancer biology is the recurrent involvement of changes to chromosome structure and/or organization within the cell.These changes are referred to as chromosome aberrations. Many forms of human cancer are so closely associated with specific chromosome aberrations that the aberrations are regarded as diagnostic for the cancer.Some chromosome aberrations result in the gain or loss of chromosomal material (numerical changes), whilst others result in a reorganization of chromosomal material (structural changes).Numerical changes alter the copy number of genes in the genome and numerical changes bring together genes that are usually separated within the non-cancer genome. The interaction between these new ‘neighbours’ often leads to the generation of gene products that drive the cell to form a cancer. Knowledge of such gene products provides an opportunity to develop new therapies for treatment of cancers. In addition, for many human cancers there is a correlation between the presence of certain chromosome aberrations and the clinical outcome of the tumor and/or the tumor’s response to therapy. For this reason many chromosome aberrations have prognostic value and this information may be used by clinicians to determine the most appropriate therapy.

Molecular cytogenetics is an exciting area of research that combines molecular biology, cytogenetics and fluorescence in situ hybridization (FISH). This approach, which makes use of sophisticated fluorescence microscopy techniques, allows us to look closely at the chromosomal organization of individual tumors and thus to identify cancer-associated chromosome aberrations.

Cytogenetic studies of dog cancers have be hindered by difficulties in identifying the chromosomes. We have developed a series of reagents and techniques that allow us to identify all dog chromosomes with confidence. These reagents include a set of whole chromosome paint probes and a genome-wide panel of single locus FISH probes. We have also isolated a number of canine cancer-associated genes.

We are now using our reagents to look closely at the chromosomal changes associated with a variety of canine cancers. We have conducted a detailed cytogenetic analysis of canine lymphoma and have identified chromosomal aberrations that suggest some of the mechanisms leading to pathogenetically important events are evolutionarily conserved. We have also identified chromosome aberrations that have not been reported for the corresponding human disease. These regions of the genome may thus contain novel cancer-associated genes. In addition, we have identified chromosome aberrations that appear to be correlated with increased survival and so may soon be in a position to offer prognostic aides to cancer diagnoses.

This work is supported by CHF grants 2038, 2214 and 2254.

Biographical Sketch

Dr. Matthew Breen graduated with honours in Genetics from the University of Liverpool, U.K. in 1987. He completed his PhD, working on cytogenetics in 1990. Dr. Breen was employed as a Post Doctoral research scientist in Molecular Genetics at the Medical Research Council’s Human Genetics Unit in Edinburgh, where he was responsible for developing improved fluorescence in situ hybridization techniques as part of the Human Genome Mapping Project. Dr. Breen then spent four years working for the Australian Thoroughbred industry, based at the University of Queensland, Brisbane Australia. In 1996 Dr. Breen returned to the U.K. where his laboratory developed molecular cytogenetics reagents, resources and techniques for application to canine genome mapping, comparative cytogenetics and cancer studies. In 1998 Dr. Breen was awarded membership of ther Institute of Biology and the title of Chartered Bioloigist.

In 2002 Dr. Breen relocated his laboratory to NCSU’s College of Veterinary Medicine as part of their Genomics initiative. His research interests continue to focus on the genomics, genome mapping and the comparative aspects of canine cancer.