Cell Journal (Jan 2010)
Recurrent Regional Allelic Imbalance in Chromosome 15 in Rat Endometrial Adenocarcinomas
Abstract
Objective: Animals of the inbred BDII rat strain are genetically predisposed to endometrialadenocarcinomas (EAC) and can be used to model human cancer. From our previousstudies, 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 inthe short arm and gains in the long arm. Since cytogenetic events lead to allelic imbalanceand/or loss of heterozygosity (AI/LoH) in RNO15, it was subjected to a detailed analysiswith polymorphic microsatellite markers spanning the entire chromosome.Materials and Methods: BDII/Han females were crossed to males from two other inbredrat strains known to have low incidence of EAC (BN/Han and SPRD-Cu3/Han). DNA extractedfrom F1, F2 and backcross offspring were used in this studies. Our final markerpanel consisted of 36 markers.Results: The analysis showed that AI/LoH was common in EAC tumors and was concentratedto four well-defined regions along the chromosome. Two of these regions were closeto the distal end of the short arm; one region was in the middle of the chromosome, probablyspanning the centromere; and the fourth region was located distally in the long arm.Conclusion: According to the Rat Genome Project (RGP), the number of genes in these regionsapproached 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 chromosomalaberrations. 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).
