Mini- and microsatellite mutations in radiation-induced acute myeloid leukaemia in the CBA/H mouse.

ABSTRACT

Radiation-induced acute myeloid leukaemia (AML) in the CBA/H mouse is a clonal disorder and therefore amenable to the analysis of genetic instability during radiation leukaemogenesis. The genotype of a single minisatellite and 20 microsatellite loci was compared in tail and leukaemic spleen DNA prepared from the same mouse. Somatic mutation at the Ms6-hm minisatellite locus was nearly seven times higher (27%, 4/15) than the spontaneous germline mutation rate (4%). Only 1/15 AMLs exhibited microsatellite mutations, but 5/20 loci were mutated in the same AML, indicating that it was deficient in mismatch repair. Thus, whereas somatic minisatellite mutations, which are associated with complex intra-allelic gene conversion events, occur at a very high rate in the radiation-induced AMLs, microsatellite instability, which has been associated with the acquisition of the replication error repair (RER+) phenotype, is infrequent but detectable.