Molecular characterization of the genomic breakpoints in a case of t(3;21)(q26;q22).
The t(3;21)(q26;q22) is a recurring chromosomal abnormality in blastic crisis of chronic myelogenous leukemia (CML) and in therapy-related myelodysplastic syndrome and acute leukemia. In order to clarify the genetic recombination mechanism underlying the t(3;21), we molecularly cloned the breakpoints and determined their nucleotide sequence in a case of CML in blastic crisis with t(3;21). Near the breakpoint on chromosome 21, three homopyrimidine (CT)-rich sequences were found. We also identified a sequence homologous to the topoisomerase II binding and cleavage consensus sequence surrounding the breakpoint on chromosome 3, and two topoisomerase II binding and cleavage consensus sequences near the breakpoint on chromosome 21. In addition, around the breakpoint on chromosome 21, four chi-like sequences, potential consensus signals for activating recombination, were found. There were no Alu sequences or antigen receptor gene-like heptamer/nonamer signal sequences within the breakpoints on chromosomes 3 and 21. The breakpoints were found adjacent to the topoisomerase II binding and cleavage consensus sequence or the homopyrimidine-rich sequence. Furthermore, the chi-like sequences and the homopyrimidine-rich sequence were detected on chromosome 21 but not on chromosome 3. Genes Chromosomes Cancer 26:92-96, 1999.
Hirai
H
H
Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. hhirai-tky@umin.ac.jp
Ogawa
S
S
Kurokawa
M
M
Yazaki
Y
Y
Mitani
K
K
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D004250:DNA Topoisomerases, Type II; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics; D008969:Molecular Sequence Data; D011743:Pyrimidines; D017422:Sequence Analysis, DNA; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D011743:Pyrimidines; D004250:DNA Topoisomerases, Type II