Microsatellite marker analysis of allelic imbalance in a rat fibrosarcoma model

Abstract

Fibrosarcomas were induced by subcutaneous injections of DMBA (7,12-dimethylbenz[a]-anthracene) in progeny from a cross between the inbred rat strains BN/Han and LE/Mol. Twenty-one of 34 treated animals (62%) developed fibrosarcomas at the injection site. The tumor DNA was analyzed for allelic imbalance that would be indicative of amplification or deletion of genetic material. In order to cover the entire length of the rat linkage map, including all 20 autosomes and the X chromosome, 215 polymorphic microsatellite markers were selected. The markers were grouped into panels of 6–12 markers, which could be analyzed simultaneously on polyacrylamide gels after fluorescent PCR amplification. Numerous cases of allelic imbalance were revealed using the panels on the fibrosarcoma material. Most of them involved markers situated on rat chromosome 1 and 2, suggesting that genes located on these chromosomes are important in sarcomagenesis. The development of microsatellite marker panels such as those described will greatly facilitate future analysis of rat tumors by genome-wide scanning.