Characterization of the translocation breakpoint sequences of two DEK-CAN fusion genes present in t(6;9) acute myeloid leukemia and a SET-CAN fusion gene found in a case of acute undifferentiated leukemia.
The t(6;9) associated with a subtype of acute myeloid leukemia (AML) was shown to generate a fusion between the 3' part of the CAN gene on chromosome 9 and the 5' part of the DEK gene on chromosome 6. The same part of the CAN gene appeared to be involved in a case of acute undifferentiated leukemia (AUL) as well, where it was fused to the SET gene. Genomic sequences around the translocation breakpoint were determined in two t(6;9) samples and in the case of the SET-CAN fusion. Although coexpression of myeloid markers and terminal deoxynucleotidyl transferase was shown to be one of the characteristics of t(6;9) AML, no addition of random nucleotides at the translocation breakpoint could be found. In addition, the breakpoint regions did not reveal heptamer-nonamer sequences, purine-pyrimidine tracts, a chi-octamer motif, or Alu repeats. The sequence in which the translocation breakpoints occurred was enriched in A/T. Notably, the specific introns in which clustering of breakpoints occurs in DEK and CAN both contain a LINE-I element. As LINE-I elements occur with a moderate frequency in the human genome, the presence of such an element in both breakpoint regions may be more than coincidental and may play a role in the translocation process.
von Lindern
M
M
Department of Cell Biology, Erasmus University, Rotterdam, The Netherlands.
Breems
D
D
van Baal
S
S
Adriaansen
H
H
Grosveld
G
G
D000208:Acute Disease; D001483:Base Sequence; D002896:Chromosomes, Human, Pair 6; D002899:Chromosomes, Human, Pair 9; D006801:Humans; D007438:Introns / Q000235:genetics; D007938:Leukemia / Q000235:genetics*; D007951:Leukemia, Myeloid / Q000235:genetics*; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000235:genetics; D016133:Polymerase Chain Reaction; D014178:Translocation, Genetic / Q000235:genetics*
D015345:Oligonucleotide Probes