Largest Genetic Map of Cat Cancer Reveals Shared Mutations with Human Tumors

A study published in Science sequenced cancer-related genes in 493 samples from 13 different types of feline cancer to obtain the most complete oncogenome of the domestic cat. The research analyzed tumor samples and adjacent healthy tissue from domestic cats, the vast majority of which were mixed breed, from five countries.

The study involved around 20 institutions, with a large group of geneticists, oncologists, and veterinarians sequencing 978 genes related to the tumors found in these cats. These genes have a sequence and function similar to approximately 1,000 genes involved in human cancer. The tumor types analyzed ranged from osteosarcoma to pancreatic adenocarcinoma, and included various mammary carcinomas, lymphomas, bone tumors, lung cancer, skin cancer, and central nervous system tumors such as meningiomas.

The researchers identified 31 cancer driver genes that were mutated in more than one sample. Five, including classic human tumor suppressor genes such as TP53, PTEN, and FBXW7, were drivers in multiple tumor types. The most frequently mutated gene, TP53, was altered in about 33 percent of all tumors analyzed. This rate is comparable to one previously reported in a human pan-cancer study: 34 percent. Similarly, 20 percent of cat tumors in the study had lost PTEN, and a past study showed that the gene was deleted in 25 percent of human cancers.

Approximately 90% of the genes in domestic cats are homologous to those in humans, more than those in dogs or mice. The study identified seven specific genes that lead to the development of certain types of aggressive breast cancer. The most common driver gene is FBXW7. More than half of the tumors in cats have mutations in this gene. One subtype is so-called triple-negative breast cancer, which is particularly aggressive and more common in young women. In cats, it is extremely aggressive and resembles triple-negative breast cancer in women.

To test whether human drugs could be useful for pet cats with cancer, the researchers treated three-dimensional feline breast cancer organoids, or tumoroids, with human chemotherapy drugs such as vincristine and vinorelbine. They found that certain FBXW7 mutations made the cat tumoroids more sensitive to the drugs, supporting the hypothesis that existing human chemotherapy drugs may benefit feline companions with cancer.

The study reveals that 14% of feline tumors have mutations for which drugs already exist in human medicine. The work validates the One Medicine approach, emphasizing how this genetic map makes it possible to use shared genetics so that what is known from human medicine can help in veterinary medicine, and vice versa. The study not only sequences DNA, but also compares tumor tissue with healthy tissue from the same cat to rule out genetic background noise. The quality is confirmed by validating the data with cross-checking techniques and by using 3D tumoroids to test drugs in the laboratory.

The authors noted that by focusing only on the 1,000 human cancer genes, the study may be missing mutations that exist only in cats. In addition, the catalog of feline genetic variants is still in its early stages and requires further validation. Regarding detected papillomavirus, the researchers warn that being infected does not equate to having cancer, since the virus also appears in healthy cats; cofactors such as UV light are needed.