Amplification of c-MYC oncogene and point mutation of N-RAS oncogene point mutation in acute myelocytic leukemias with double minute chromosomes.

Two patients with acute myelocytic leukemia (AML) showing double minute (dmin) chromosomes were analysed to identify oncogene activation. Cytogenetic analysis showed 1-53 dmin chromosomes with the normal karyotype in the first patient and 1-84 dmin chromosomes with complex chromosome aberrations. Analysis of DNA from two patients revealed five- to tenfold amplification of c-MYC oncogene in the leukemic cells. The other sixteen oncogenes studied showed no increase in the gene content. Furthermore, a transforming gene, N-RAS was detected in the first patient by nude mouse tumorigenicity assay (in vivo selection assay). These results suggest that the amplification of c-MYC gene is common in dmin-positive AML patients and co-ordination of c-MYC and N-RAS oncogene might also play a significant role in the pathogenesis of some AML patients.