Characterization of the translocation breakpoint sequences in Philadelphia-positive acute lymphoblastic leukemia.
We have previously described a patient in whom the breakpoint occurred within the first intron of the BCR gene and have cloned the 9q+ and 22q- junctions. We have now determined the nucleotide sequence around the breakpoints on both translocation products from this patient as well as the corresponding regions from the normal chromosomes 9 and 22. We have compared the sequence with that of the breakpoint regions in the Ph1-positive leukemic patients in order to check for the presence of conserved motifs. A + T-rich sequences and ALU repeat elements are the only sequence characteristics which appear to be very common around translocation regions. The chromosome 9 ABL sequences at or adjacent to the breakpoints present in the 22q- product show homology to the consensus ALU sequence while the chromosome 22 sequences do not, suggesting a non-homologous recombination mechanism. While no sequences are deleted, there is a two-base-pair "homology" at the junction. Therefore, staggered breaks followed by ligation and repair could be part of the mechanism involved in the process of translocation in some cases of Ph1-positive ALL.
Papadopoulos
P C
PC
Leukaemia Research Fund Centre, Institute of Cancer Research, London, England.
Greenstein
A M
AM
Gaffney
R A
RA
Westbrook
C A
CA
Wiedemann
L M
LM
D001483:Base Sequence; D002892:Chromosomes, Human, Pair 22; D002899:Chromosomes, Human, Pair 9; D004249:DNA Damage; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000235:genetics; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011519:Proto-Oncogenes; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid; D014178:Translocation, Genetic
D004273:DNA, Neoplasm; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl