K-ms mutation and c-myc amplification in induction of genetic instabllity

instability of microsatellite sequences are frequently found in human tumors. In addition, minisatellite sequences, another group of highly unstable sequences, serve as sensitive markers of genetic instability. We have studied minisatellite instability in methylcholanthrene-induced mouse sarcomas. These sarcomas frequently carry the amplified c-myc gene. Seven sarcomas without the amplification and seven others with the amplification were selected randomly. Regardless of the state ofthe c-myc gene amplification, these sarcomas exhibited a varying degree of trans plantablllty in syngeneic mice. The hypervariable mouse minisatellite locus Ms6hm was found to be highly unstable, specifically among sarco mm with the amplified c-myc gene. However, chromosome Instability, as anal@ by micronucleus assay, was observed similarly for two groups of sarcomas. In addition, transversion of G to C and A to T was detected at the K-ms gene in four of the seven sarcomaswith the amplifiedc-myc gene,and thesemutationsare thoughtto be induceddirectlyby methyl cholanthrene. Thus, concomitant occurrence was observed for three seem ingly unrelated mutations, amplification of the c-myc locus, point muta don of the K-nzs gene, and instability at the hypervariable mouse minisatellite locus. The present study indicates a possible involvement of K-ms mutation and c-myc amplification in induction of genetic instabllity in methylcholanthrene-induced mouse sarcomas.