The t(11;20)(p15;q11) chromosomal translocation associated with therapy-related myelodysplastic syndrome results in an NUP98-TOP1 fusion.
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Ahuja HG, Felix CA, Aplan PD
The t(11;20)(p15;q11) chromosomal translocation associated with therapy-related myelodysplastic syndrome results in an NUP98-TOP1 fusion.
Blood. 1999 Nov 1;94(9):3258-61.
- PubMed ID
- 10556215 [ View in PubMed]
- Abstract
The NUP98 gene is involved in 3 distinct chromosomal rearrangements, t(7;11)(p15;p15), t(2;11)(q31;p15), and inv(11)(p15q22); all of these NUP98 rearrangements have been identified in the malignant cells of patients with therapy-related acute myelogenous leukemia or myelodysplastic syndrome (t-AML/MDS). Here we report the cloning and characterization of a t(11;20)(p15;q11) translocation from patients with t-MDS. The breakpoint on chromosome 11p15 targets the NUP98 gene and results in the separation of the N-terminal FXFG repeats from the RNA-binding domain located in the C-terminus. The breakpoint on chromosome 20q11 occurs within the gene encoding human DNA topoisomerase I (TOP1). As a result, a chimeric mRNA encoding the NUP98 FXFG repeats fused to the body of DNA topoisomerase I is produced. These results indicate that NUP98 is a recurrent target in therapy-related malignancies, and that TOP1 is a previously unrecognized target for chromosomal translocations.