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/promoter were analyzed for loss of heterozygosity to identify chromosomal regions which potentially contain genetic loci involved in multistep tumorigenesis. A broad pattern of complete and partial loss of heterozygosity or allelic imbalance was observed with frequent loss of heterozygosity/partial loss of heterozygosity of loci on chromosomes 1, 5, 7, 8, and 12. In tumors from Mus domesticus x Mus spretus F1 mice a strong preference for loss of the domesticus allele of H19 on chromosome 7 was observed, whereas loss of heterozygosity/partial loss of heterozygosity on chromosome 8 involved preferential loss of spretus alleles. In tumors from reciprocal crosses with Mus castaneus, the maternal chromosome 7 H19 allele was preferentially lost irrespective of whether it was domesticus or castaneus, strongly suggesting the involvement of an imprinted gene(s) in tumor progression.
Held
W A
WA
Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York 14263.
Pazik
J
J
O'Brien
J G
JG
Kerns
K
K
Gobey
M
M
Meis
R
R
Kenny
L
L
Rustum
Y
Y
D000483:Alleles; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics*; D015139:Blotting, Southern; D001947:Breeding; D005260:Female; D017353:Gene Deletion; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic
D000952:Antigens, Polyomavirus Transforming