Recurrent Regional Allelic Imbalance in Chromosome 15 in Rat Endometrial Adenocarcinomas

Animals of the inbred BDII rat strain are genetically predisposed to endometrial adenocarcinomas (EAC) and can be used to model human cancer. From our previous studies, it was obvious that some chromosomes were selectively involved in EAC development; one of them was rat chromosome (RNO) 15, in which there were often losses in the short arm and gains in the long arm. Since cytogenetic events lead to allelic imbalance and/or loss of heterozygosity (AI/LoH) in RNO15, it was subjected to a detailed analysis with polymorphic microsatellite markers spanning the entire chromosome. BDII/Han females were crossed to males from two other inbred rat strains known to have low incidence of EAC (BN/Han and SPRD-Cu3/Han). DNA extracted from F1, F2 and backcross offspring were used in this studies. Our final marker panel consisted of 36 markers. The analysis showed that AI/LoH was common in EAC tumors and was concentrated to four well-defined regions along the chromosome. Two of these regions were close to the distal end of the short arm; one region was in the middle of the chromosome, probably spanning the centromere; and the fourth region was located distally in the long arm. According to the Rat Genome Project (RGP), the number of genes in these regions approached 300. According to a database search, about 80 of these genes could be considered “cancer-related” and they were potential candidates to be targets for the observed chromosomal aberrations. Among the cancer-related genes, there were Anxa7 (Region I), Bmp4, Lgals3, Cdkn3 (Region II), Rb1, Ddx26, Clu, Bnip3, Nkx3.1 (Region III), and Gpc5 (Region IV).