Multigenic control of skin tumour development in mice

Different inbred mouse strains vary greatly in their susceptibility to tumour development in a variety of tissues. Intraspecific and interspecific crosses can, therefore, be used to map the loci that control this predisposition. Crosses of Mus musculus with Mus spretus are highly resistant to tumour development in the skin, liver, lung and lymphoid system. M. spretus, therefore, has dominantly acting resistance loci, which we have attempted to map. More than 350 interspecific backcross mice were followed for 18 months to assess susceptibility to development of chemically induced papillomas and carcinomas. The results were analysed using a combination of MAPMAKER/QTL analysis and multiple regression analysis for the determination of linkage in multigenic quantitative traits. The results showed clearly that at least three genes on chromosomes 5 and 7 control resistance to tumour development. Importantly, some genes confer resistance to benign tumours but they have relatively little effect on malignant progression. This suggests the existence of different classes of benign tumours: those that are capable of tumour progression and those that have only a very low probability of becoming malignant. Identification of these genes will improve our understanding of mechanisms of carcinogenesis and may provide a novel route to the identification of "low-penetrance' human tumour susceptibility genes.