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Blood, Vol. 94 No. 9 (November 1), 1999:
pp. 3258-3261
The t(11;20)(p15;q11) Chromosomal Translocation Associated With
Therapy-Related Myelodysplastic Syndrome Results in an
NUP98-TOP1 Fusion
Harish G. Ahuja,
Carolyn A. Felix, and
Peter D. Aplan
From the Departments of Medicine, Pediatrics, and
Cancer Genetics, Roswell Park Cancer Institute,
Buffalo, NY; the Division of Oncology,
The Children's Hospital of Philadelphia, University
of Pennsylvania School of Medicine, Philadelphia, PA; and
the Division of Hematology/Oncology, Children's
Hospital of Buffalo, Buffalo, NY.
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.

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