Written | 2004-12 | Junko Horiguchi Yamada |
Department of Oncology, Institute of DNA Medicine, The Jikei University, School of Medicine, Tokyo, Japan |
Identity |
HGNC (Hugo) | TOP1 |
HGNC Alias name | Scl-70 antigen |
HGNC Previous name | topoisomerase (DNA) I |
LocusID (NCBI) | 7150 |
Atlas_Id | 320 |
Location | 20q12 [Link to chromosome band 20q12] |
Location_base_pair | Starts at 41028822 and ends at 41124486 bp from pter ( according to GRCh38/hg38-Dec_2013) [Mapping TOP1.png] |
Local_order | centromer to telomer |
Fusion genes (updated 2017) | Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands) |
MRFAP1 (4p16.1) / TOP1 (20q12) | NUP98 (11p15.4) / TOP1 (20q12) | SENP6 (6q14.1) / TOP1 (20q12) | |
SHROOM2 (Xp22.2) / TOP1 (20q12) | TOP1 (20q12) / C17orf64 (17q23.2) | TOP1 (20q12) / CDH4 (20q13.33) | |
TOP1 (20q12) / NUP98 (11p15.4) | TOP1 (20q12) / PZP (12p13.31) |
DNA/RNA |
Note | The sequence is split into 21 exons over 85kbp. Introns are 0.2-30 kbp in size. |
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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) |
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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 |
Note | |
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 |
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Oncogenesis | NUP98-TOP1 fusion protein has been proved to have leukemogenic activities independent of topoisomerase activity. |
Breakpoints |
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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. |
Bibliography |
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 |
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 |
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 |
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 |
Structure of the human type I DNA topoisomerase gene. |
Kunze N, Yang GC, Dölberg M, Sundarp R, Knippers R, Richter A |
The Journal of biological chemistry. 1991 ; 266 (15) : 9610-9616. |
PMID 1851751 |
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, Billström R, Mitelman F, Johansson B |
Genes, chromosomes & cancer. 2002 ; 34 (2) : 249-254. |
PMID 11979559 |
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 |
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 |
Citation |
This paper should be referenced as such : |
Yamada, JH |
TOP1 (topoisomerase (DNA) 1) |
Atlas Genet Cytogenet Oncol Haematol. 2005;9(1):12-14. |
Free journal version : [ pdf ] [ DOI ] |
Other Leukemias implicated (Data extracted from papers in the Atlas) [ 4 ] |
del(20q) in myeloid malignancies
dic(17;20)(p11.2;q11.2) t(4;11)(q21;p15) NUP98/RAP1GDS1 t(11;20)(p15;q11) NUP98/TOP1 |
Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 3 ] |
t(12;20)(p13;q12) TOP1/PZP
t(17;20)(q23;q12) TOP1/C17orf64 t(20;20)(q12;q13) TOP1/CDH4 |
External links |
REVIEW articles | automatic search in PubMed |
Last year publications | automatic search in PubMed |
© Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Fri Jan 1 19:03:15 CET 2021 |
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