t(11;20)(p15;q11) NUP98/TOP1
2005-03-01 Junko Horiguchi-Yamada , Tetsuaki Sekikawa Affiliation1.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. | 52 |
| 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 |
| 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). | 0 |
| 12874791 | 2003 | Both NUP98/TOP1 and TOP1/NUP98 transcripts are detected in a de novo AML with t(11;20)(p15;q11). | 0 |
| 16939812 | 2006 | Retroviral integration site analysis identifies ICSBP as a collaborating tumor suppressor gene in NUP98-TOP1-induced leukemia. | 0 |
| 15100157 | 2004 | NUP98-topoisomerase I acute myeloid leukemia-associated fusion gene has potent leukemogenic activities independent of an engineered catalytic site mutation. | 0 |
| 12645654 | 2003 | Generation of the NUP98-TOP1 fusion transcript by the t(11;20) (p15;q11) in a case of acute monocytic leukemia. | 0 |
| 10556215 | 1999 | The t(11;20)(p15;q11) chromosomal translocation associated with therapy-related myelodysplastic syndrome results in an NUP98-TOP1 fusion. | 0 |
| 15036893 | 2004 | A t(11;20)(p15;q11) may identify a subset of nontherapy-related acute myelocytic leukemia. | 0 |
| 15951287 | 2005 | Screening for NUP98 rearrangements in hematopoietic malignancies by fluorescence in situ hybridization. | 0 |
| 18223676 | 2008 | Acceleration of chronic myeloproliferation by enforced expression of Meis1 or Meis3 in Icsbp-deficient bone marrow cells. | 0 |
| 30378313 | 2018 | [Molecular Characteristics and Clinical Features of Adults with NUP98 Fusions in Acute Myeloid 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
