Gliomas are the most common form of brain tumors in humans and the second most common in dogs. In an effort to understand the genetic drivers underlying these brain tumors, researchers surveyed the dog genome and found three genes
that could contribute to risks for tumor development.
Around 10 to 20 percent of all childhood brain tumors are gliomas that originate in the brain stem. These brain tumors are devastating and rarely curable, with the 5-year survival rate for brain and nervous system cancer around 33 percent. As such, there is a tremendous need for research that can elucidate the genes and pathways involved in these tumors, and hopefully bring about new therapies for patients.
Humans and dogs share 84 percent of their DNA, making dogs extremely valuable models of human diseases. Researchers often rely on dog models to study diseases such as retinal diseases and cancers like gliomas. Interestingly, some dog breeds are more susceptible to gliomas than others. These include the brachycephalic breeds such as Boxer, Bulldog, and Boston Terrier. By contrast, the Pug and Pekingese breeds have a lower risk for developing the tumor.
Recognizing the value of this similarity, scientists at Uppsala University in Sweden set out to find candidate genes that may underlie the risk for gliomas in dogs. They hoped the same genes can inform glioma pathogenesis in humans.
“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 same risk factors for glioma could also be present in other breeds and the way to identify the genomic region would be to compare genetic markers from dogs diagnosed with glioma from several breeds to healthy controls. Based on this we then performed several genetic analyses to narrow down the region in the genome,” said Katarina Truvé, first study author.
Led by Kerstin Lindblad-Toh, the team performed a genome wide scan across 25 dog breeds. They used blood samples from 39 dogs with gliomas, and 141 healthy dogs. In screening for genes most often mutated only in dogs with gliomas, the team identified three candidate suspects: CAMKK2, P2RX7 and DENR. These three genes were found to be highly associated with glioma susceptibility.
Among the three gene candidates, two have already been implicated in cancer: CAMKK2 shows reduced expression in both dog and human brain tumors, and P2RX7 mutations have been identified in human cancer patients.
The team believes that one or more of these genes are involved in glioma development. They hope further tests into the function of these genes will elucidate the mechanism behind glioma formation in humans. Such results could yield new targets for treatment in humans and dogs.
Additional source: Science Daily