The inv(11)(p15q22) chromosome translocation of de novo and therapy-related myeloid malignancies results in fusion of the nucleoporin gene, NUP98, with the putative RNA helicase gene, DDX10.
The inv(11)(p15q22) is a recurrent chromosomal abnormality associated with de novo and therapy-related myeloid malignancies. Here we report the molecular definition of this chromosomal aberration in four patients. Positional cloning showed the consistent rearrangement of the DDX10 gene on chromosome 11q22, which encodes a putative RNA helicase. The translocation targets the NUP98 gene on 11p15, a member of the FG peptide repeat nucleoporin family. In DDX10 and NUP98, the inv(11) breakpoints occurred within two introns of each gene and the two genes merged in-frame to produce the chimeric transcripts characteristic of this translocation. Although two reciprocal chimeric products, NUP98-DDX10 and DDX10-NUP98, were predicted, only NUP98-DDX10 appears to be implicated in tumorigenesis. DDX10 is predicted to be involved in ribosome assembly. NUP98 has been identified as a nuclear pore complex protein and a target of chromosomal translocation in acute myeloid leukemia through the t(7;11)(p15;p15) translocation. The predicted NUP98-DDX10 fusion protein may promote leukemogenesis through aberrant nucleoplasmic transport of mRNA or alterations in ribosome assembly.
Arai
Y
Y
Radiobiology Division, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
Hosoda
F
F
Kobayashi
H
H
Arai
K
K
Hayashi
Y
Y
Kamada
N
N
Kaneko
Y
Y
Ohki
M
M
D000595:Amino Acid Sequence; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D001483:Base Sequence; D002880:Chromosomes, Human, Pair 11; D015321:Gene Rearrangement; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009190:Myelodysplastic Syndromes / Q000139:chemically induced / Q000235:genetics*; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins / Q000235:genetics*; D020365:RNA Helicases; D012316:RNA Nucleotidyltransferases / Q000235:genetics*; D014178:Translocation, Genetic
D008565:Membrane Proteins; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; C093350:nuclear pore complex protein 98; D012316:RNA Nucleotidyltransferases; D020365:RNA Helicases