**11. Dogs as cancer models**

An animal model is an indispensable model to investigate the pathogenesis, molecular mechanisms of tumor initiation and development and to test novel treatments. Scientists have increasing interest in dog disease models in recent years. Dogs may have many advantages to be used as disease models compared with the most popular model species such as mouse and rat [42]. Dogs are the most popular companion animals globally and are the second in medical surveillance and preventative health care after humans [42]. Dogs are more similar to humans such as in genetics, immune systems, body size. Meanwhile, pet dogs share living environment with their owners, thus receiving similar environment factors. There is, for example, a gap between mouse model and chimpanzee models in clinical trials. There is no doubt that mice contribute a lot to novel drug development. However, it is also true that many drugs work during trials on mice but fail in human clinical trials because of difference in physiology between these two species.

Breed dogs have in general low genetic diversity due to two bottleneck events in history: one is domestication from grey wolf around 15,000 years ago, and another one is strong artificial selection in order to fix certain traits of breeds during the breed formation in the past ~200 years [43]. This low genetic diversity results in many genetic diseases/disorders, such as osteosarcoma in Rottweiler, elbow dysplasia in Labrador Retriever, and medial patellar luxation in Chihuahua [44, 45]. According to a study of Farrell et al., there are 396 hereditary disorders identified in 215 officially recognized dog breeds in the United Kingdom [46]. Many of these disorders also occur in humans, which makes those dogs potentially valuable disease models to investigate the pathogenesis of those disorders. Low genetic diversity within each dog breed makes mapping of causal variants of those diseases easier in dogs than that in humans. Much smaller number of SNPs are needed to identify the genomic region that is associated with an inherited disease in dogs in comparison to humans because of the low genetic diversity and large haplotype blocks [42]. This facilitates unraveling the genetic basis of inherited disease.

In rodents, thyroid carcinoma usually has a follicular architecture but does not have the morphological or cytological characteristics used in the diagnosis of papillary carcinomas in humans [37]. Canine thyroid carcinoma is more similar to human thyroid carcinoma in morphology of histology in comparison to thyroid carcinoma in rodents. GLPs with familial FCCs can be a valuable disease model to elucidate the molecular mechanism underlying tumor initiation and development with driver mutations in the *GNAS* gene.
