PMID- 7803279 OWN - NLM STAT- MEDLINE DCOM- 19950202 LR - 20211203 IS - 0007-1048 (Print) IS - 0007-1048 (Linking) VI - 88 IP - 2 DP - 1994 Oct TI - Sequential acquisition of trisomy 8 and N-ras mutation in acute myeloid leukaemia demonstrated by analysis of isolated leukaemic colonies. PG - 338-42 AB - 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. FAU - Price, C M AU - Price CM AD - Centre of Cell and Molecular Biology, Chester Beatty Laboratories, Institute of Cancer Research, London. FAU - Marshall, C J AU - Marshall CJ FAU - Bashey, A AU - Bashey A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Br J Haematol JT - British journal of haematology JID - 0372544 SB - IM MH - Adult MH - Base Sequence MH - *Chromosomes, Human, Pair 8 MH - Female MH - Genes, ras/*genetics MH - Humans MH - In Situ Hybridization, Fluorescence MH - Leukemia, Myelomonocytic, Acute/*genetics MH - Molecular Sequence Data MH - Neoplastic Stem Cells/physiology MH - *Point Mutation MH - Polymerase Chain Reaction MH - Proto-Oncogene Mas MH - Time Factors MH - *Trisomy MH - Tumor Cells, Cultured EDAT- 1994/10/01 00:00 MHDA- 1994/10/01 00:01 CRDT- 1994/10/01 00:00 PHST- 1994/10/01 00:00 [pubmed] PHST- 1994/10/01 00:01 [medline] PHST- 1994/10/01 00:00 [entrez] AID - 10.1111/j.1365-2141.1994.tb05028.x [doi] PST - ppublish SO - Br J Haematol. 1994 Oct;88(2):338-42. doi: 10.1111/j.1365-2141.1994.tb05028.x.