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Sequential acquisition of trisomy 8 and N‐ras mutation in acute myeloid leukaemia demonstrated by analysis of isolated leukaemic colonies
Author(s) -
Price Cathy M.,
Marshall Christopher J.,
Bashey Asad
Publication year - 1994
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1994.tb05028.x
Subject(s) - trisomy , point mutation , biology , mutation , trisomy 8 , microbiology and biotechnology , fluorescence in situ hybridization , chromosome , genetics , aneuploidy , myeloid , karyotype , cancer research , gene
Summary. 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.