A novel gene, NSD1, is fused to NUP98 in the t(5;11)(q35;p15.5) in de novochildhood acute myeloid leukemia

The recurrent translocation t(5;11)(q35; p15.5) associated with a 5q deleti on, del(5q), has been reported in childhood acute myeloid leukemia (AML). W e report the cloning of the translocation breakpoints in de novo childhood AML harboring a cryptic t(5;11)(q35;p15.5). Fluorescence in situ hybridizat ion (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 n ovel gene, NSD1. The NSD1 gene has 2596 amino acid residues and a 85% homol ogy 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, NSDI-NUP98, was also detected by reverse transcriptase-polymera se chain reaction. This is the first report in which the novel gene NSD1 ha s been implicated in human malignancy.