Key human bladder cancer genes discovered in cats and dogs
Researchers have identified genes responsible for the spontaneous development of bladder carcinoma in animals. They will be suitable for creating targeted cancer therapies in humans.Canadian researchers sequenced spontaneous bladder carcinomas in cats and dogs, formed by natural processes without external influence. The analysis showed the presence of common genes characteristic of human urothelial carcinoma. The similarity of the genes could be used to develop therapies for this cancer.
The researchers collaborated with veterinary pathologists from 17 countries to obtain bladder cancer tissue samples from cats and dogs diagnosed with the disease. The researchers compared mutated and healthy animal tissues to identify genes that had changed in cancer cells.
Of the 60 driver genes in which mutations are associated with the development of bladder carcinoma in humans, three were found in cancer cells in cats (TP53, FAT1 and NRAS), and two in dogs (ARID1A and KDM6A). The TP53 gene, which is also frequently altered in muscle-invasive bladder cancer in humans, was more frequently mutated in cats.
Meanwhile, in dogs, most mutations were fixed in the BRAF gene. In humans, such changes are often seen in melanoma cells, but in bladder cancer they are seen in only 3% of patients. This specificity will allow dogs to be used as model animals for drug development and clinical trials for therapy of cancer with this rare form of mutation.
Studying spontaneous cancer cases in animals and cross-species comparisons helps identify cancer-causing genetic events among the "noise" from genetic variation. If a mutation is conserved across multiple species, it is more likely to be biologically relevant to cancer development, the scientists explain.
Cross-species comparisons provide a basis for developing new treatments, allowing researchers to identify promising candidate genes to prioritize therapy development.