t(11;20)(p15;q11) NUP98/TOP1

2005-03-01   Junko Horiguchi-Yamada , Tetsuaki Sekikawa 

1.Dept. of Oncology, Institute of DNA Mecidine, The Jikei University, School of Medicine, Tokyo, Japan

Clinics and Pathology

Disease

Phenotype stem cell origin

myeloid, positive for CD34, 33, 13, HLA-DR.

Etiology

either therapy-related or de novo
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Table 1
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Leukemic cells have characteristics of type II myeloblasts with numerous granules. Several large nucleoli are seen in nuclei.(Wright-Giemmsa staining)(x 1,000)

Genes Involved and Proteins

Gene name
NUP98 (nucleoporin 98 kDa)
Location
11p15.4
Note
The NUP98 gene is fused to a number of genes through chromosomal translocation. The breakpoints in NUP98 gene span six introns (intron 9-14). Of particular notice, one type of translocation occurs in a specific intron. As for t(11;20), all four cases have the breakpoint in intron 13 of NUP98 gene.
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Gene name
TOP1 (topoisomerase (DNA) 1)
Location
20q12
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Protein description
Topoisomerase 1 is a ca.100 kDa protein with 765 amino acids; contains NLS in the N-term, a core domain which recognizes its binding sequences, a link domain which connects the core and catalytic domains, and the catalytic domain in the C-term.

Result of the Chromosomal Anomaly

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Structural diagrams of NUP98, TOP1, and fused chimeras. Fused protein has N-terminal of NUP98, which contains two FG repeats, and the core, link and catalytic domains of TOP1. Gene product of TOP1/NUP98 (150kD) has been demonstrated, but the fused protein of TOP1/NUP98 has not been examined.

Oncogenesis

NUP98-TOP1 fusion protein has been proved to be leukemogenic in mice.

Bibliography

Pubmed IDLast YearTitleAuthors
109590882000Potential role for DNA topoisomerase II poisons in the generation of t(11;20)(p15;q11) translocations.Ahuja HG et al
126456542003Generation of the NUP98-TOP1 fusion transcript by the t(11;20) (p15;q11) in a case of acute monocytic leukemia.Chen S et al
151001572004NUP98-topoisomerase I acute myeloid leukemia-associated fusion gene has potent leukemogenic activities independent of an engineered catalytic site mutation.Gurevich RM et al
128747912003Both NUP98/TOP1 and TOP1/NUP98 transcripts are detected in a de novo AML with t(11;20)(p15;q11).Iwase S et al
119795592002Expression of NUP98/TOP1, but not of TOP1/NUP98, in a treatment-related myelodysplastic syndrome with t(10;20;11)(q24;q11;p15).Panagopoulos I et al
150368932004A t(11;20)(p15;q11) may identify a subset of nontherapy-related acute myelocytic leukemia.Potenza L et al

Summary

Fusion gene

NUP98/TOP1 NUP98 (11p15.4) TOP1 (20q12) M t(11;20)(p15;q12)|NUP98/TOP1 NUP98 (11p15.4) TOP1 (20q12) TIC
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t(11;20)(p15;q11) G-banding..

Citation

Junko Horiguchi-Yamada ; Tetsuaki Sekikawa

t(11;20)(p15;q11) NUP98/TOP1

Atlas Genet Cytogenet Oncol Haematol. 2005-03-01

Online version: http://atlasgeneticsoncology.org/haematological/1155/t(11;20)(p15;q11)-nup98-top1

External Links