My last blog discussed the complexity of inherited cancer predisposition syndromes. A concept was introduced about the types of genetic mutations that can predispose a dog (or human) for cancer. Some genetic mutations are passed through the blood line, while other genetic mutations are NOT passed on to the next generation. Today, I would like to address this idea in greater detail. These genetic mutations are called germline and somatic.
Germline mutations are passed through the generations. These are the mutations that show different modes of inheritance: dominant, recessive, X-linked, and mitochondrial. Germline mutations are present in the sex cells (sperm and/or egg) and can affect multiple pups in a litter. These are the mutations Paw Print Genetics offers testing for, which may impact breeding practices. Breeders equipped with this information have the power to reduce, and maybe even eliminate, these mutations from breeding lines.
Somatic mutations are genetic changes in the cells of the individual. These mutations are usually not present at birth and can occur in any cell or organ over time. These are usually due to environmental influences, although the exact triggers are often unclear. The chance for a dog to acquire a somatic mutation gets higher as the dog gets older. This is because the environmental impact on the body accumulates with age. Regardless, these mutations cannot be passed on to the next generation. The presence of these genetic mutations should not impact breeding practices at all. Somatic mutations most often predispose or specifically cause cancer. The somatic mutation starts in a single cell. As that cell replicates, the somatic mutation is replicated with it. That single cell eventually becomes a cluster of many cells, which can form a tumor or cancerous growth. So although it’s a genetic mutation, it is not inherited. Incidentally, in humans, knowing the somatic mutation in a tumor may affect the type of therapy prescribed.
An example of a canine hereditary cancer predisposition syndrome is renal cystadenocarcinoma and nodular dermatofibrosis, which is found in German shepherd dogs. It predisposes the dog to renal (kidney) cancer. This condition is a combination of abnormal growth in the kidneys and the skin. Affected dogs usually present with firm bumps or lumps under the surface of the skin, more commonly located on the limbs and head. Signs of kidney problems can include increase in water consumption, increased urination, depression and weight loss. Extra fibrous tissue on the kidneys may cause them to become enlarged and abnormally shaped. The kidneys may become so large that the affected dog’s abdomen may become distended. The disease typically presents over the age of five.
This disease is the result of genetic changes that are both germline and somatic. Genetic testing is only available for the germline mutation which is inherited as an autosomal dominant condition. Genetic testing of the BHD gene in German shepherd dogs will determine whether a dog carries the mutation and is at risk for renal cystadenocarcinoma and nodular dermatofibrosis. Reliable genetic testing for the germline mutation is important for determining breeding practices, especially in this later-onset disease. Breeding of affected dogs is not recommended, as there is a 50% risk for offspring to inherit the mutation and will be at high risk for renal cell cancer. German shepherd dogs that are not found to have the mutation have no increased risk of having affected pups.
People quite often ask me if a disease/condition is genetic or not. What they are really asking is if it is inherited or not. It is important to know what genetic change is inherited, so a testing strategy can be designed.
Photo attribution: Wikimedia Commons