Long-range mapping of the Philadelphia chromosome by pulsed-field gel
electrophoresis
CA Westbrook, CM Rubin, JJ Carrino, MM Le Beau, A Bernards and JD Rowley
University of Chicago, Department of Medicine, IL 60637.
The Philadelphia chromosome (Ph1) of chronic myelogenous leukemia (CML)
contains sequences from chromosome 9, including the ABL protooncogene, that
have been translocated to the breakpoint cluster region (bcr) of chromosome
22, giving rise to a bcr-ABL fusion gene, whose product has been implicated
in the genesis of CML. Although chromosome 22 translocation breakpoints in
CML virtually always occur within the 5.8- kilobase (kb) bcr, chromosome 9
breakpoints have been identified within the known limits of ABL in only a
few instances. For a better understanding of the variability of the
breakpoints on chromosome 9, we studied the CML cell line BV173. Using
pulsed-field gel electrophoresis (PFGE), large-scale maps of the t(9;22)
junctions were constructed. The chromosome 9 breakpoint was shown to have
occurred within an ABL intron, 160 kb upstream of the v-abl homologous
sequences, but still 35 kb downstream of the 5'-most ABL exon. bcr-ABL and
ABL-bcr fusion genes were demonstrated on the Ph1 and the 9q+ chromosomes,
respectively; both of these genes are expressed. These results suggest that
the 9;22 translocation breakpoints in CML consistently occur within the
limits of the large ABL gene. RNA splicing, sometimes of very large
regions, appears to compensate for the variability in breakpoint location.
These studies show that PFGE is a powerful new tool for the analysis of
chromosomal translocations in human malignancies.
Volume 71,
Issue 3,
pp. 697-702,
03/01/1988
Copyright © 1988 by The American Society of Hematology
