Study finds new genetic cause of canine bladder cancer

New research into bladder cancer in dogs could make it easier for vets to detect the disease at an early stage and offer targeted treatment.

Previous research showed that 85% of canine urothelial carcinomas (a type of bladder cancer) share a specific mutation in a gene named BRAF. This mutation, known as V595E, results in abnormal activation of a genetic signalling pathway which leads to uncontrolled cellular growth, or proliferation.

“Essentially, BRAF V595E generates an abnormal protein that instructs the cells to keep dividing, forming a tumour,” said Matthew Breen from North Carolina State University, corresponding author of the new research. “So if this single nucleotide substitution in the BRAF gene is detected in 85% of all canine urothelial carcinomas, why is it not in all of them?

“Pathologists see no difference between those cancers with this mutation and those without, so what’s going on with that other 15%?”

Examining 28 canine urothelial carcinomas without the BRAF V595E nucleotide substitution, the research team at North Carolina State University found that 13 of the 28 cases (46%) had a different type of mutation, where a small number of nucleotides had been deleted.

“Evidence from human cancers suggests that these deletions would generate abnormal proteins that can initiate uncontrolled cellular proliferation and result in a tumour — essentially the same end result as V595E,” explained Rachael Thomas, lead author of the study. “We have developed a laboratory assay that can simultaneously detect both the substitution and deletion mutations, to expand our opportunity for early detection of these cancers in dogs.”

Being able to differentiate between cancers based on their underlying genetic changes may also lead to more precise — and more effective — treatment.

Next, the researchers will work to identify drugs that will effectively target canine bladder cancers with these recently discovered mutations. They will also continue searching for potential genetic causes for the remaining 7% of canine bladder cancer cases.

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