Sequential acquisition of trisomy 8 and N-ras mutation in acute myeloid leukaemia demonstrated by analysis of isolated leukaemic colonies.
Specific chromosomal aberrations and point mutations of the N-ras proto-oncogene are characteristic genetic alterations in acute leukaemias. However, the relationships between these two different genetic changes are unclear. Here we have determined the order of genetic events in a patient with acute myeloid leukaemia characterized by trisomy 8 and a point mutation of N-ras at codon 12 (N12-cys) and codon 61 (N61-his). 30 colonies obtained by in vitro clonogenic assay of leukaemic cells from a patient with AML were individually analysed for the presence of trisomy 8 and each of two different N-ras mutations by fluorescence in situ hybridization (FISH) and the polymerase chain reaction (PCR). Trisomy 8 was detected in 25/26 evaluable colonies. 19/26 colonies contained the N12-cys mutation. The N61-his mutation was not detected in any of the colonies obtained. All the colonies with the N12 cys mutation were also trisomic from chromosome 8, whereas 6/25 colonies with trisomy 8 had no N-ras mutation. These data suggest that trisomy 8 was acquired before N12 cys mutation in the pathogenesis of this leukaemia and that two genetic events can co-operate within a single subclone.
Price
C M
CM
Centre of Cell and Molecular Biology, Chester Beatty Laboratories, Institute of Cancer Research, London.
Marshall
C J
CJ
Bashey
A
A
D000328:Adult; D001483:Base Sequence; D002898:Chromosomes, Human, Pair 8; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics*; D008969:Molecular Sequence Data; D014411:Neoplastic Stem Cells / Q000502:physiology; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D013997:Time Factors; D014314:Trisomy; D014407:Tumor Cells, Cultured