Dog genetics helps cancer researchers shine a light on brain tumors.
Gliomas are a particularly aggressive form of brain tumor. They develop quickly and are rarely curable.
Survival rates vary depending on the type of glioma and the age of the patient. The 2-year survival rate is less than 15 percent for the most common form of glioma, called glioblastoma.
Certain dog breeds are also susceptible to this group of cancers. Brachycephalic breeds - dogs with broad, short skulls - such as boxers, Boston terriers, and bulldogs, are known to have an elevated risk.
Gliomas are the most common form of malignant primary brain tumor in humans and the second most common in dogs. The tumor's cellular makeup in dogs is strikingly similar to that found in humans and occurs at a similar rate in both species - 15 cases per 100,000 dogs and 20 per 100,000 humans.
Dogs and cancer research
Using dogs as models for human disease has proven to be incredibly useful. They share much of our DNA, live in similar environments, and get many of the same diseases. Also, because they have been bred with care, mapping diseases through their genetic tree is easier than it is in humans.
The research team, led by the study's author Katarina Truvé, delved into the genetics of these breeds in an attempt to single out genes that might be responsible for certain breeds' susceptibility to gliomas.
The different breeds that show a predisposition to gliomas are closely related, but not all closely related breeds display the same high susceptibility.
For instance, pugs and Pekingese do not have the same level of risk for gliomas as boxers and bulldogs. Because of these differences, the team hoped that the genomic regions responsible could be identified by comparing the breeds.
"In our study, we hypothesized that since the brachycephalic dog breeds with elevated risk are closely related, we would be able to identify a genomic region shared by those breeds."
The team managed to pinpoint the relevant genes by comparing genetic markers from different breeds of dog with glioma to healthy dogs. Based on the findings, the team performed a number of complex genetic analyses to narrow down the search to specific regions of the genome.
In total, the team investigated the genomes of 25 dog breeds. Blood was taken from 39 dogs diagnosed with glioma and 141 control dogs.
Glioma genes uncovered
The results, published this week in PLOS Genetics, detail three genes found to be associated with tumor susceptibility - CAMKK2, P2RX7, and DENR.
Although the exact roles of the genes are not fully understood, they are known to be present in both dogs and humans:
- CAMKK2: This gene is mostly expressed in the brain and is thought to be involved in learning and memory, growth and movement of neurons, and the formation of new synapses
- P2RX7: This gene codes for a receptor that is thought to play a role in cell death, regulating the movement of molecules between and within cells, and inflammation. It is known to play a part in certain cancers, but its exact role in disease is not yet understood
- DENR: The protein coded by this gene is thought to help initiate the process of turning mRNA into proteins. It is also associated with an increased rate of certain cancers.
To further investigate their roles, the activity of the genes was measured in tumor tissue and compared with normal tissue. Prof. Karin Forsberg Nilsson, professor at the Department of Immunology, Genetics and Pathology and Science for Life Laboratory, was involved in the analysis of the brain tissue.
"We found that especially one of the genes [CAMKK2] showed reduced activity in tumor tissue. These results indicate that further investigations of the role of these three genes in glioma development would be of interest, with potential benefit to both dog and human."
Prof. Karin Forsberg Nilsson
Further study of these three genes will hopefully deepen our understanding of glioma in both species of mammal and lead to more effective treatments for this destructive disease.