Genetic Study of Cat Cancers Reveals Parallels to Human Breast Cancer

An international research team, with participation of the University of Bern, has conducted the world's first comprehensive genetic study of cancer in domestic cats. The study shows that some of the genetic changes in cat tumors closely resemble those found in human cancers, opening up new perspectives for developing targeted cancer therapies, particularly for breast cancer.

Researchers from the Institute of Animal Pathology at the Vetsuisse Faculty of the University of Bern, the Ontario Veterinary College (Canada) and the Wellcome Sanger Institute (UK) examined the genomes of various cancer types in cats in unprecedented detail. They identified genetic changes that drive cancer development in cats and show remarkable similarities to those in human cancer. The results were recently published in the journal Science.

The study is based on the genetic analysis of 13 different types of cancer in cats. Researchers analyzed leftover normal and cancerous tissue samples collected during routine treatment from nearly 500 cats across five countries. The researchers analyzed around 1,000 genes that are direct counterparts of known human cancer-related genes and compared the key mutations in these genes across cats, dogs and humans.

The study provides the world's first freely accessible database for future research into the genetics of feline cancer. The analyses revealed that TP53 is the most frequently mutated gene in cat cancer, similar to humans. Certain genetic changes promote cancer development in cats, and some of these changes also occur more frequently at the same positions in the genome of cats and humans, at so-called mutation hotspots.

The genetic analyses revealed some unexpected findings in mammary tumors. Mammary tumors in cats resemble the phenotype of triple-negative human breast cancer, leading researchers to suspect that cats also have the known BRCA1 mutation. Surprisingly, however, this was not the case. Instead, the researchers primarily found changes in the FBXW7 gene, which is also associated with an unfavorable prognosis in human breast cancer.

This research identified seven driver genes that led to the development of cancer when mutated in feline mammary carcinomas. The most common driver gene was FBXW7 and over 50 percent of the cat tumors had a change in this gene. The second most common driver gene was PIK3CA, seen in 47 percent of cat mammary carcinoma tumors. This is also a genetic change found in human breast cancer, where it is treated with PI3K inhibitors.

In an earlier study, human leukemia cells with the inactive FBXW7 gene were found to be particularly responsive to certain anti-cancer drugs such as vinca alkaloids. Building on this knowledge, the team tested these drugs on MAM tumoroids, three-dimensional cell culture models of mammary tumors. In vitro, vinca alkaloids were markedly more effective in feline tumoroids with FBXW7 mutations compared to tumoroids without these mutations.

Similarities to human driver mutations were also seen across blood, bone, lung, skin, gastro-intestinal, and central nervous system tumors. The COMPATH platform based at the University of Bern, together with expertise in the field of data-driven precision medicine at the Bern Center for Precision Medicine (BCPM) played an important role in analyzing the feline mammary tumors.

Cancer is one of the leading causes of illness and death in cats. Domestic cats are the second most prevalent pet globally after dogs. According to estimates, around 25 percent of households in Switzerland alone own a cat, and up to 1.5 million animals were living in the country last year. Almost a quarter of all UK households own at least one cat, and with over 10 million cats living in the UK, they are now about as popular as dogs as pets.

Because cats share our households and environmental exposures, studying cat cancers within a "One Health" framework can reveal how environmental factors influence cancer risk and why cancer develops in both cats and humans. This demonstrates how, in line with the "One Health" approach, findings from veterinary medicine can inform human medicine and vice versa.