Elevated frequency of loss of heterozygosity in mammary tumors arising in mouse mammary tumor virus/neu transgenic mice

Loss of heterozygosity (LOH) analysis was performed on 62 mammary tumors th at were induced in (BALB/c x C57BL/6)F-1 mouse mammary tumor virus/neu tran sgenic mice. Eighty-six simple sequence length polymorphism markers were us ed to cover all of the somatic chromosomes. Frequency of LOH was observed t o be significant for chromosomes 4 (50%). 19 (32%), and 8 (21%). On chromos ome 4, at least three distinct regions of allelic deletions could be identi fied: one proximal to 22 cM; the second close to the p16(INK4a)/p15(INK4b) locus, which is commonly deleted in various tumors; and the third one in th e proximity of Mom1. The frequency of LOH on chromosome 19 was the same for the four markers used. Our data suggested the presence of two distinct LOH loci, one proximal to 47 cM and the other at the distal region. On chromos ome 8, possibly two distinct LOH loci could be recognized, one around 52 cM and the other one at 67 cM or distal to it, These regions map close to E-c adherin (Cdh1) and M-cadherin (Cdh15) loci, respectively. Because LOH sites are thought to harbor tumor suppressor genes, this allelotype screening ha s allowed the mapping of putative tumor suppressor genes that may be implic ated, in collaboration with the erbB-2/neu oncogene, in the development of mammary tumors in these transgenic mice.