Analysis of genetic changes in rat endometrial carcinomas by means of comparative genomic hybridization

Animals of the BDII inbred rat strain are known to be genetically predispos ed to endometrial adenocarcinoma (EAC). Using them as models of human EACs. we studied tumors arising in Fl and F2 progeny from BDII animals crossed t o animals from two other inbred strains. in which EACs were quite rare. In order to identify chromosomal regions exhibiting DNA copy number changes. c omparative genomic hybridization (CGH) was applied in a series correspondin g to 27 different solid tumors, most of which were classified as EACs. from these animals. The main findings from the study were that, although many d ifferent chromosomes were involved in copy number variation. some of the ch anges detected were recurrent and quite specific. Among specific changes fo und were gains in rat chromosome (RNO) regions 4q12 similar to q22. 6q14 si milar to q16. and whole chromosome arms in some of the small metacentric ch romosomes (e.g.. RNO14. 16. and 18). RNO10 was involved in gain in the term inal and proximal regions. Each of these regions contains previously identi fied cancer-related genes representing possible candidates to be involved i n the development of EAC. Furthermore. it was observed that there were clea r differences in the pattern of copy number changes between tumors occurrin g in the two different crosses, and also between solid tumors and cell cult ures. Endometrial cancer is the most common human gynecological cancer. hut not much is known about specific genetic changes influencing this disease. Two genetic alterations that have been reported from human endometrial can cer are amplification of the ERBB2 gent: and mutations in the 12 codon of t he KRAS gene. One case of Erbb2 amplification was found but there were no K ras mutations in the rat material studied. We conclude that molecular genet ic analysis of the rat BDII model will provide important new information ab out EAC in mammals. (C) 2001 Elsevier Science Inc. All rights reserved.