The t(11;20)(p15;q11) chromosomal translocation associated with therapy-related myelodysplastic syndrome results in an NUP98-TOP1 fusion

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 rearr angements have been identified in the malignant cells of patients with ther apy-related acute myelogenous leukemia or myelodysplastic syndrome (t-AML/M DS). 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 FXF G repeats from the RNA-binding domain located in the C-terminus, The breakp oint on chromosome 20q11 occurs within the gene encoding human DNA topoisom erase I (TOP1). As a result, a chimeric mRNA encoding the NUP98 FXFG repeat s fused to the body of DNA topoisomerase I is produced. These results indic ate that NUP98 is a recurrent target in therapy-related malignancies, and t hat TOP1 is a previously unrecognized target for chromosomal translocations . (C) 1999 by The American Society of Hematology.