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

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

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

Clinics and Pathology

Disease

Acute myelogenous leukemia, Therapy-related MDS (RAEB, RAEB-t)

Phenotype stem cell origin

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

Etiology

either therapy-related or de novo

Table 1

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.

Gene name

TOP1 (topoisomerase (DNA) 1)

Location

20q12

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

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.

Highly cited references

Pubmed ID	Year	Title	Citations
27889185	2016	NUP98 Fusion Proteins Interact with the NSL and MLL1 Complexes to Drive Leukemogenesis.	59
10556215	1999	The t(11;20)(p15;q11) chromosomal translocation associated with therapy-related myelodysplastic syndrome results in an NUP98-TOP1 fusion.	14
15100157	2004	NUP98-topoisomerase I acute myeloid leukemia-associated fusion gene has potent leukemogenic activities independent of an engineered catalytic site mutation.	13
16939812	2006	Retroviral integration site analysis identifies ICSBP as a collaborating tumor suppressor gene in NUP98-TOP1-induced leukemia.	7
15951287	2005	Screening for NUP98 rearrangements in hematopoietic malignancies by fluorescence in situ hybridization.	5
12874791	2003	Both NUP98/TOP1 and TOP1/NUP98 transcripts are detected in a de novo AML with t(11;20)(p15;q11).	3
18223676	2008	Acceleration of chronic myeloproliferation by enforced expression of Meis1 or Meis3 in Icsbp-deficient bone marrow cells.	2
12645654	2003	Generation of the NUP98-TOP1 fusion transcript by the t(11;20) (p15;q11) in a case of acute monocytic leukemia.	2
11979559	2002	Expression of NUP98/TOP1, but not of TOP1/NUP98, in a treatment-related myelodysplastic syndrome with t(10;20;11)(q24;q11;p15).	2
30378313	2018	[Molecular Characteristics and Clinical Features of Adults with NUP98 Fusions in Acute Myeloid Leukemia].	0
28249294	2016	Coexpression of NUP98/TOP1 and TOP1/NUP98 in de novo Acute Myeloid Leukemia with t(11;20)(p15;q12) and t(2;5)(q33;q31).	0
15036893	2004	A t(11;20)(p15;q11) may identify a subset of nontherapy-related acute myelocytic leukemia.	0

Article Bibliography

Pubmed ID	Last Year	Title	Authors
10959088	2000	Potential role for DNA topoisomerase II poisons in the generation of t(11;20)(p15;q11) translocations.	Ahuja HG et al
12645654	2003	Generation of the NUP98-TOP1 fusion transcript by the t(11;20) (p15;q11) in a case of acute monocytic leukemia.	Chen S et al
15100157	2004	NUP98-topoisomerase I acute myeloid leukemia-associated fusion gene has potent leukemogenic activities independent of an engineered catalytic site mutation.	Gurevich RM et al
12874791	2003	Both NUP98/TOP1 and TOP1/NUP98 transcripts are detected in a de novo AML with t(11;20)(p15;q11).	Iwase S et al
11979559	2002	Expression 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
15036893	2004	A 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

R banding image, courtesy Thomas Guéry-Hemsen (Centre Hospitalier Orléanais Universitaire)

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