Paul C and Borghild T
Petersen Foundation
Research Laboratory

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Genetics

Canine brain tumors as a platform for discovery:

In addition to providing translational models for assessment and development of novel therapies, animal models of cancer provide a wonderful opportunity for investigation of genetic and environmental factors involved in the initiation and progression of tumors, including those affecting the brain; from these discoveries, the identification of potential future targets for therapeutic intervention is a logical progression. Dogs are relatively outbred when looking at a population of animals (Yorkshire Terrier to German Shepherd), and certainly so compared to most traditional rodent models of cancer. However within specific inbred lines and breeds there are well documented higher incidences of specific cancers. Overrepresented breeds for brain tumors include many brachycephaic dogs for gliomas, such as Boxers, Bostons and Bulldogs, and Golden retrievers and Boxers for meningiomas. Interestingly, the incidence of brain tumors in cats is much lower than dogs and the vast majority of these tumors are meningiomas. Most feline meningiomas are more benign than their canine or human counterparts, and multiple tumors are more common compared to dog and human. From an investigational and comparative perspective, the reasons why cats have a low incidence of gliomas, and a high incidence of multiple, relatively benign meningiomas may be just as relevant to cancer biology as the striking similarities between the more aggressive gliomas seen in humans and dogs. Both the canine and feline genome are now available, together with a rapidly expanding collection of species specific investigational tools such as oligonucleotide microarrays, tissue arrays, proteomic arrays and validated antibodies to an increasing spectrum of cancer related epitopes. Mapping cancer related genes in brain tumor predisposed breeds is potentially much easier than in the more diverse human population, and the potential for discovery of new cancer pathways and targets for diagnosis and treatment is great.

Preliminary data for canine brain tumors has already defined similarities with human tumors, beyond histology and imaging, including abnormalities in growth factors and their receptors (eg VEGF, PDGF, EGF), surface receptors such as IL-13 R2a, tumor suppressor genes, telomerase activity, and stem cell-like populations of cells within gliomas. Genomic analysis of canine tumors has revealed not only similarities between humans and dogs, but also intriguing differences opening new opportunities for cancer gene discovery through comparative studies. Defining canine brain tumors at the molecular level will not only provide insight into the basic biology of CNS tumors, but also provide a rational basis for the choice of specific tumor types, and even individual patients, for assessment of novel targeted therapies.

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A map of chromosomal losses (red) and gains (green) in canine meningiomas.

In collaboration with geneticists at North Carolina School of Veterinary Medicine, analysis of canine brain tumors for chromosomal abnormalities has identified potential genes that may be important in both human and canine tumors. View publication

Ongoing genetic research..How you can help

In collaboration with The Petersen Foundation Brain Tumor Laboratory run by Dr Dickinson at the UC Davis Veterinary School, Dr Banasch’s laboratory have been attempting to uncover the genetic cause for brachycephaly in dogs and subsequently to try and find genes linked to brachycephaly that may increase the risk of developing a brain tumor.

Dr Banasch has already identified candidate genes for brachycephaly. View publication As part of the associated search for genes involved with brain tumors, the lab is collecting DNA from animals known or suspected to have a brain tumor. Identification of these genes may allow for:

1) Selective breeding to reduce the frequency of brain tumors in brachycephalic dogs.

2) Possible new therapies targeting defective genes.

Without DNA samples from affected brachycephalic dogs, we will not be able to map the abnormal genes. The more samples we have the easier, quicker and more accurate the search will be.

If you have a dog that is suspected, or confirmed to have a brain tumor, Dr Dickinson and Dr Banasch will be very happy to discuss how you can help to eliminate this disease from the brachycephalic breeds.

The Neurology/Neurosurgery service at UC Davis also has state of the art treatments for brain tumors and clinical trials that your animal may be eligible to enroll in. These trials have already had some exciting successes and are supported by the National Institutes of Health (NIH) . Financial assistance to cover MR imaging, diagnostic and treatment procedures is available for dogs enrolled in the trials. Dr Dickinson will be happy to discuss all the treatment options with you and your veterinarian, and to review any diagnostic information such as MRI scans.

If you have a dog with a suspected brain tumor, you can contact Dr Dickinson either directly, or through Toni Beelard, the Neurology/Neurosurgery service coordinator:

Dr Dickinson e-mail: pjdickinson@ucdavis.edu

Toni Beelard (Tel) 530 754 0606
UC Davis Veterinary Medical Teaching Hospital
UC Davis, School of Veterinary Medicine
Davis, CA 95616

(Tel) 530 752 1393