An epistatic interaction controls the latency of a transgene-induced mammary tumor

Previous studies from our laboratory demonstrated that the latency, tumor g rowth, and metastatic progression of polyoma middle T-induced mammary tumor in an FVB/NJ inbred mouse background could be significantly altered by the introduction of different genetic backgrounds. In this study we extend the se findings by mapping a number of interacting quantitative trait loci resp onsible for the changes in phenotype. Introduction of the I/LnJ inbred gene tic background into the FVB/NJ-PyMT animal significantly accelerated the ap pearance of the primary tumor (35 vs. 57 days postnatal, p < 10(-7)). A bac kcross mapping panel was established, and loci responsible for the tumor ac celeration were detected on Chrs 15 and 9. Examination of the genotype/phen otype correlation revealed that the FVB/NJ but not the I/LnJ allele of the Chr 15 locus was associated with tumor acceleration and was conditional on the presence of I/LnJ allele on Chr 9. These loci, designated Apmt1 and Apm t2, map to homologous regions associated with LOH in human breast cancer. T hese results suggest that allelic variants of genes in these regions may co ntribute to age of onset in human breast cancer.