Dark Colored Dogs Highlight Cancer's Complexity

04/17/2013

The breeding process that has led to the more than 300 distinct domestic dog breeds has created a type of species diversity ideal for the study of genetic diseases. Individual dog breeds, and sometimes even individual subtypes within the breed, are often at increased risk for specific diseases. Since dogs within each breed are quite similar, looking for differences between affected dogs and unaffected dogs can be a highly effective way to isolate the gene responsible for a given illness. 

Standard poodles, for example, are at risk of an aggressive type of cancer known as squamous cell carcinoma of the digit (SCDD). SCDD causes bone disease in the toes, and susceptible dogs often have multiple recurrences, once after another. However, not all poodles are equally susceptible to SCDD. Dark colored poodles are at high risk of this cancer, while light colored dogs are almost never affected.

The complex pattern of SCDD risk seen in Standard Poodles means that multiple gene mutations are likely involved in its development. Recently, with the support of the AKC Canine Health Foundation, a group of researchers set out to determine where exactly those mutations might be. They succeeded. In a study published in the March 2013 issue of PLOS One, scientists from UCLA and the National Institutes of Health identified two areas of the canine genome where changes seemed to play important roles in the cancer’s pathogenesis. The first mutation, located within in the KIT Ligand (KITLG) locus, seemed to explain the increased risk of SCDD seen in Standard Poodles and several other breeds.  The second, found in the melanocortin 1 receptor (MC1R) locus, seemed to protect the light colored dogs.

The research results suggest that the KITLG locus is likely responsible for increasing susceptibility to SCDD in Standard Poodles, and it also plays a clear role in the development of SCDD in two other susceptible breeds. The results also suggest that interactions between KITLG and MC1R are probably required for these cancers to progress.  That makes a certain amount of sense. MC1R is not only responsible for certain differences in coat color. It is known to be associated with skin cancer risk in dogs, horses, and humans as well.

An increased understanding of SCDD is not, however, the only take home message from this study. This research also provides additional, and compelling, evidence of the important role that domestic dogs can play in the understanding of canine and human disease. Humans have spent centuries breeding hundreds of distinct types of dogs to fill our needs for trackers, companions, and even guardians. Now, thanks to the advances of science, it looks like they have a new way to help us.

This work was funded by AKC Canine Health Foundation grant 1052-A.

Publication:

A Copy Number Variant at the KITLG Locus Likely Confers Risk for Canine Squamous Cell Carcinoma of the Digit (PLOS Genetics is an open access journal providing free access to the full publication)

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