Loss of heterozygosity in spontaneous and chemically induced tumors of the B6C3F1 mouse.
The B6C3F1 mouse is used worldwide to gauge the carcinogenic hazard posed by chemicals to humans. An assessment of the ability of this rodent model to predict human neoplasia requires an evaluation of similarities and differences in the genetics of tumor formation between these two species. We examined 142 spontaneous and chemically-induced liver tumors isolated from the B6C3F1 mouse for losses of heterozygosity (LOH) at 78 polymorphic loci and compared these results to genetic changes known to occur in human hepatocellular carcinoma. Approximately a third of the 142 mouse tumors exhibited LOH, suggesting that tumor suppressor gene inactivation may be involved in the formation of mouse liver tumors. Most of the LOH observed was restricted to seven chromosome sites and most of the tumors that underwent LOH lost alleles from only one of those seven sites. The relatively few losses seen in these mouse tumors distinguished them from clinical stage human tumors in that, in the mouse tumors, interstitial deletions appeared more frequently than losses of whole chromosomes. Only four mouse tumors lost a whole chromosome. LOH occurred at loci of the mouse genome syntenic to areas of the human genome known to harbor the Wilms', retinoblastoma, APC, MCC and DCC tumor suppressor genes; these genes have never been associated with hepatocellular carcinomas. Losses observed on chromosomes 5 and 8 (syntenic to human chromosomes 4 and 16) suggest tumor suppressor genes that are common to hepatocellular carcinomas from both species, while losses on chromosome 9 suggest involvement of a previously unidentified tumor suppressor gene.
Davis
L M
LM
Applied Genetics Laboratories Inc., Melbourne, FL.
Caspary
W J
WJ
Sakallah
S A
SA
Maronpot
R
R
Wiseman
R
R
Barrett
J C
JC
Elliott
R
R
Hozier
J C
JC
D000818:Animals; D002872:Chromosome Deletion; D016147:Genes, Tumor Suppressor; D008113:Liver Neoplasms / Q000235:genetics / Q000662:veterinary*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics*; D051379:Mice / Q000235:genetics*; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D012376:Rodent Diseases / Q000235:genetics*