Allelotype analysis of chemically induced squamous cell carcinomas in F-1 hybrids of two inbred mouse strains with different susceptibility to tumor progression

Loss of heterozygosity (LOH) at specific chromosomal loci is generally cons idered indirect evidence for the presence of putative suppressor genes. All elotyping of tumors using polymorphic markers distributed throughout the en tire genome allows the analysis of specific allelic losses. In the field of chemical carcinogenesis, the outbred SENCAR mouse has been commonly used t o analyze the multistage nature of skin tumor development. In the study rep orted here we generated F-1 hybrids between two inbred strains (SENCARB/Pt and SSIN/Sprd) derived from the SENCAR stock that differ in their susceptib ility to tumor progression. We typed 24 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate-induced squamous cell carcinomas for L OH using 56 microsatellite markers distributed among all autosomal chromoso mes. The highest percentage of LOH, 78%, was found on chromosome 7, but the re was no preferential loss of one particular allele, indicating that the p utative suppressor genes found in this area are not involved in genetic sus ceptibility. High levels of LOH were also found on chromosomes 16 (39%), 6 (29%), 4 (25%), 9 (25%), 14 (22%), 10 (20%) and 19 (20%), but with no prefe rential loss of the alleles of one strain. The chromosomal regions with LOH on mouse chromosomes 4, 6, 7, 9, 10, 14, 16 and 19 correspond to regions i n the human genome where LOH has been reported and have been suggested to h arbor tumor suppressor genes.