Atlas of Genetics and Cytogenetics in Oncology and Haematology
TOP1 (topoisomerase (DNA) 1)
| Identity |
| HGNC (Hugo) | TOP1 |
| Location | 20q12-q13.1 |
| Location_base_pair | Starts at 39090876 and ends at 39186540 bp from pter ( according to hg18-Mar_2006) [Mapping] |
| Local_order | centromer to telomer |
| DNA/RNA |
| Note | The sequence is split into 21 exons over 85kbp. Introns are 0.2-30 kbp in size. |
 | |
| The star denotes intron 7 where chromosome translocation occurs. | |
| Description | 21 exons with 20 introns |
| Transcription | 3.8 kb (single band) |
| Pseudogene | 2 pseudogenes. TOP1P1 on chromosome 1q23-q24, and TOP1P2 on chromosome 22q12-q13.1. |
| Protein |
| Note | type I DNA topoisomerase, EC (5.99.1.2) |
 | |
| The arrow indicates the breaking point of translocation, and the star denotes the sites of point mutation. | |
| Description | 765 amino acids, about 100kDa; 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. |
| Expression | Ubiquitous. The expression level is up-regulated along with cell proliferation signals. |
| Localisation | Nucleus |
| Function | TOP1 catalyzes the breaking and rejoining of single DNA strand. |
| Homology | The core and catalytic domains are conserved between the human and S.cerevisiae enzyme. |
| Mutations |
| Somatic | Translocation of chromosome t(11;20)(p15;q12) has been reported in hematological malignancies (see below). Point mutations with amino acid substitution in the catalytic domain have been implicated in irinotecan-resistance. |
| Implicated in |
| Entity | t(11;20)(p15;q12) |
| Disease | de novo acute myeloid leukemia, acute monocytic leukemia, therapy-related myelodysplastic syndrome/leukemia(t-MDS/AML) |
| Prognosis | poor (?) |
| Hybrid/Mutated Gene | NUP98/TOP1 |
 | |
| Oncogenesis | NUP98-TOP1 fusion protein has been proved to have leukemogenic activities independent of topoisomerase activity. |
| Breakpoints |
 | |
| The breakpoints locate in intron 7, causing the fusion protein to lack the N-terminal 169 amino acids.The breakpoints locate in the repetitive elements or close to them which exist in intron 7 of TOP1 gene. | |
| To be noted |
| Point mutations W736stop and G737S were detected in lung non-small cell carcinoma. The significance of mutations in catalytic domain has been suspected to be relevant to susceptibility to irinotecan. |
| External links |
| Bibliography |
| Structure of the human type I DNA topoisomerase gene. |
| Kunze N, Yang GC, Dlberg M, Sundarp R, Knippers R, Richter A |
| The Journal of biological chemistry. 1991 ; 266 (15) : 9610-9616. |
| PMID 1851751 |
| The t(11;20)(p15;q11) chromosomal translocation associated with therapy-related myelodysplastic syndrome results in an NUP98-TOP1 fusion. |
| Ahuja HG, Felix CA, Aplan PD |
| Blood. 1999 ; 94 (9) : 3258-3261. |
| PMID 10556215 |
| Potential role for DNA topoisomerase II poisons in the generation of t(11;20)(p15;q11) translocations. |
| Ahuja HG, Felix CA, Aplan PD |
| Genes, chromosomes & cancer. 2000 ; 29 (2) : 96-105. |
| PMID 10959088 |
| 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, Fioretos T, Isaksson M, Larsson G, Billstrm R, Mitelman F, Johansson B |
| Genes, chromosomes & cancer. 2002 ; 34 (2) : 249-254. |
| PMID 11979559 |
| Point mutations in the topoisomerase I gene in patients with non-small cell lung cancer treated with irinotecan. |
| Tsurutani J, Nitta T, Hirashima T, Komiya T, Uejima H, Tada H, Syunichi N, Tohda A, Fukuoka M, Nakagawa K |
| Lung cancer (Amsterdam, Netherlands). 2002 ; 35 (3) : 299-304. |
| PMID 11844605 |
| Generation of the NUP98-TOP1 fusion transcript by the t(11;20) (p15;q11) in a case of acute monocytic leukemia. |
| Chen S, Xue Y, Chen Z, Guo Y, Wu Y, Pan J |
| Cancer genetics and cytogenetics. 2003 ; 140 (2) : 153-156. |
| PMID 12645654 |
| Both NUP98/TOP1 and TOP1/NUP98 transcripts are detected in a de novo AML with t(11;20)(p15;q11). |
| Iwase S, Akiyama N, Sekikawa T, Saito S, Arakawa Y, Horiguchi-Yamada J, Yamada H |
| Genes, chromosomes & cancer. 2003 ; 38 (1) : 102-105. |
| PMID 12874791 |
| NUP98-topoisomerase I acute myeloid leukemia-associated fusion gene has potent leukemogenic activities independent of an engineered catalytic site mutation. |
| Gurevich RM, Aplan PD, Humphries RK |
| Blood. 2004 ; 104 (4) : 1127-1136. |
| PMID 15100157 |
| A t(11;20)(p15;q11) may identify a subset of nontherapy-related acute myelocytic leukemia. |
| Potenza L, Sinigaglia B, Luppi M, Morselli M, Saviola A, Ferrari A, Riva G, Zucchini P, Giacobbi F, Emilia G, Temperani P, Torelli G |
| Cancer genetics and cytogenetics. 2004 ; 149 (2) : 164-168. |
| PMID 15036893 |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 12-2004 | Junko Horiguchi Yamada |
| Department of Oncology, Institute of DNA Medicine, The Jikei University, School of Medicine, Tokyo, Japan |
| Citation |
| This paper should be referenced as such : |
| Yamada JH . TOP1 (topoisomerase (DNA) 1). Atlas Genet Cytogenet Oncol Haematol. December 2004 . URL : http://AtlasGeneticsOncology.org/Genes/TOP1ID320ch20q11.html |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Sat Jun 27 16:38:42 CEST 2009 |
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