A novel gene, NSD1, is fused to NUP98 in the t(5;11)(q35;p15.5) in de novo childhood acute myeloid leukemia.
The recurrent translocation t(5;11)(q35;p15.5) associated with a 5q deletion, del(5q), has been reported in childhood acute myeloid leukemia (AML). We report the cloning of the translocation breakpoints in de novo childhood AML harboring a cryptic t(5;11)(q35;p15.5). Fluorescence in situ hybridization (FISH) analysis demonstrated that the nucleoporin gene (NUP98) at 11p15.5 was disrupted by this translocation. By using 3'--rapid amplification of complementary DNA ends (3'-RACE) polymerase chain reaction, we identified a chimeric messenger RNA that results in the in-frame fusion of NUP98 to a novel gene, NSD1. The NSD1 gene has 2596 amino acid residues and a 85% homology to the murine Nsd1 with the domain structure being conserved. The NSD1 gene was localized to 5q35 by FISH and is widely expressed. The reciprocal transcript, NSD1-NUP98, was also detected by reverse transcriptase--polymerase chain reaction. This is the first report in which the novel gene NSD1 has been implicated in human malignancy. (Blood. 2001;98:1264-1267)
Jaju
R J
RJ
LRF Molecular Haematology Unit, Nuffield Department of Clinical Laboratory Sciences, University of Oxford, United Kingdom. rina.jaju@ndcls.ox.ac.uk
Fidler
C
C
Haas
O A
OA
Strickson
A J
AJ
Watkins
F
F
Clark
K
K
Cross
N C
NC
Cheng
J F
JF
Aplan
P D
PD
Kearney
L
L
Boultwood
J
J
Wainscoat
J S
JS
D000208:Acute Disease; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002880:Chromosomes, Human, Pair 11; D002895:Chromosomes, Human, Pair 5; D020732:Cytogenetic Analysis; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007951:Leukemia, Myeloid / Q000209:etiology / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins / Q000235:genetics*; D014178:Translocation, Genetic
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; C093350:nuclear pore complex protein 98; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C113272:NSD1 protein, human