) Tumor suppressor genes play a key role in oncogenesis. We performed a genome-wide search for loss of heterozygosity (LOH) in 90 mouse mammary carcinomas, induced by expression of the MMTV/v-Ha-ras transgene in hybrid mice, and found evdince for two novel tumor suppressor genes that may be the homologs of genes important in human cancer locted at chromosome 1 p32-36. We have designted these genes Loh3 and Loh5. The long-term goals of these studies are the positional cloning of these genes and their human homologs. In support of these objectives, two specific aims are to be attacked here: 1. Perform a detailed genetic linkage analysis using backcrossed transgenic mice to identify a narrow genetic map interval that contains Loh3. 2. Continue high resolution mapping of Loh5 based on allelic loss in tumors. New, single nucleotide polymorphism markers will be derived for the region of mouse chromosome 4 that contains this locus.
