GENETIC-ANALYSIS OF LIVER TUMORIGENESIS IN SV40 T-ANTIGEN TRANSGENIC MICE IMPLIES A ROLE FOR IMPRINTED GENES

Liver tumors from interspecific hybrid, transgenic mice containing the SV40 early region linked to a mouse major urinary protein enhancer/pr omoter were analyzed for loss of heterozygosity to identify chromosoma l regions which potentially contain genetic loci involved in multistep tumorigenesis. A broad pattern of complete and partial loss of hetero zygosity or allelic imbalance was observed with frequent loss of heter ozygosity/partial loss of heterozygosity of loci on chromosomes 1, 5, 7, 8, and 12, In tumors from Mus domesticus x Mus spretus F-1 mice a s trong preference for loss of the domesticus allele of H19 on chromosom e 7 was observed, whereas loss of heterozygosity/partial loss of heter ozygosity on chromosome 8 involved preferential loss of spretus allele s, In tumors from reciprocal crosses with Mas castaneus, the maternal chromosome 7 H19 allele was preferentially lost irrespective of whethe r it was domesticus or castaneus, strongly suggesting the involvement of an imprinted gene(s) in tumor progression,