Comparative analyses of tumour related genes in dogs as model systems for human cancer

The canine genome offers a wide field for genetic studies on various areas like e.g. phenotypic diversity, heredity and diseases including cancer. The cancers seen in pet dogs are spontaneously developing as opposed to cancers of laboratory rodents. This suggests that the mechanisms of development in canine tumours could be comparable to humans. It is generally believed that dogs develop cancer twice as frequently as humans, and that the presentation, histology and biology of several canine cancers is similar to humans. Most canine cancers progress more rapidly than their human counterparts permitting a better monitoring of the tumour state. The canine cancers are more akin to human cancers than rodent tumours in terms of patient size and cell kinetics allowing better comparison of medical examinations like e.g. ultrasonography. Additionally, dogs show similar characteristics of physiology and metabolism for most organ systems and drugs, which allows better comparability of modalities e.g. surgery, radiation and chemotherapy.In this thesis, the canine HMGA1, HMGB1, ZNF331, and CCND1 genes were characterised on various levels including their cDNA structure, partial genomic DNA structure, and their expression patterns. Their corresponding proteins were predicted by in silico analyses and gene identity analyses were carried out comparing these characterised genes with their corresponding counterparts of various other species. Additionally, the gene loci of these genes and of six other genes were defined by FISH analyses. Further on, to analyse if known molecular mechanisms involved in human cancers are existent in dogs as well, thirteen canine fibrosarcomas, two feline fibrosarcomas, and eleven canine melanomas were screened for hot-spot mutations of the NRAS and KRAS2 genes. No such mutations could be detected, suggesting that these mutations do not play a major role in the analysed neoplasias.