Expression of NUP98/TOP1, but not of TOP1/NUP98, in a treatment-related myelodysplastic syndrome with t(10;20;11)(q24;q11;p15).
Panagopoulos, Ioannis LU ; Fioretos, Thoas LU ; Isaksson, Margareth LU ; Larsson, Gun ; Billström, Rolf ; Mitelman, Felix LU
and Johansson, Bertil
LU
(2002)
In Genes, Chromosomes and Cancer
34(2).
p.249-254
- Abstract
- The t(11;20)(p15;q11) is a rare but recurrent translocation that so far has been described in only four acute myeloid leukemias (AMLs), two treatment-related myelodysplastic syndromes (t-MDSs), and one case of polycythemia vera. Recently, the t(11;20) was shown to result in a fusion of the NUP98 and TOP1 genes, with expression of the NUP98/TOP1 chimera encoded by the der(11)t(11;20), but not of the reciprocal TOP1/NUP98 on the der(20)t(11;20). The genomic breakpoints were subsequently mapped to introns 13 and 7 of NUP98 and TOP1, respectively. We present here a t-MDS with a three-way variant translocation, t(10;20;11)(q24;q11;p15), that generates a der(11)t(11;20) but not a der(20)t(11;20), strongly suggesting that the der(11) harbors the... (More)
- The t(11;20)(p15;q11) is a rare but recurrent translocation that so far has been described in only four acute myeloid leukemias (AMLs), two treatment-related myelodysplastic syndromes (t-MDSs), and one case of polycythemia vera. Recently, the t(11;20) was shown to result in a fusion of the NUP98 and TOP1 genes, with expression of the NUP98/TOP1 chimera encoded by the der(11)t(11;20), but not of the reciprocal TOP1/NUP98 on the der(20)t(11;20). The genomic breakpoints were subsequently mapped to introns 13 and 7 of NUP98 and TOP1, respectively. We present here a t-MDS with a three-way variant translocation, t(10;20;11)(q24;q11;p15), that generates a der(11)t(11;20) but not a der(20)t(11;20), strongly suggesting that the der(11) harbors the critical genetic rearrangement. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed a NUP98/TOP1 fusion in which exon 13 of NUP98 was fused in-frame with exon 8 of TOP1. Extra long (XL) genomic PCR and subsequent sequence analyses showed that the breakpoint in NUP98 occurred at nucleotide (nt) 3461 of intron 13, close to a MER (medium reiteration frequency interspersed repetitive element) repeat, and that the breakpoint in TOP1 was at nt 1436 of intron 7, downstream of a MIR (mammalian-wide interspersed repeats) repetitive element. Genomic XL PCR did not amplify the reciprocal TOP1/NUP98, nor was this chimera expressed, as expected from the cytogenetic finding. The present results provide further support for the involvement of the NUP98/TOP1 transcript, but not of the reciprocal one, in the development of MDS/AML. Furthermore, the three cases genomically characterized to date have all been treatment-related and have all harbored breakpoints in intron 13 of NUP98 and intron 7 of TOP1, suggesting that these introns are susceptible to chemotherapy-induced breakage. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/108411
- author
- Panagopoulos, Ioannis
LU
; Fioretos, Thoas
LU
; Isaksson, Margareth
LU
; Larsson, Gun
; Billström, Rolf
; Mitelman, Felix
LU
and Johansson, Bertil
LU
- organization
- publishing date
- 2002
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Chromosomes, Human, Pair 20 : genetics, DNA Topoisomerases, Type I : biosynthesis, Type I : genetics, Female, Middle Age, Molecular Sequence Data, Myelodysplastic Syndromes : chemically induced, Myelodysplastic Syndromes : genetics, Nuclear Pore Complex Proteins : biosynthesis, Neoplasm Proteins : genetics, Nuclear Pore Complex Proteins : genetics, Support, Non-U.S. Gov't, Translocation (Genetics) : genetics, Pair 11 : genetics, Pair 10 : genetics, Human : genetics, Case Report, Base Sequence : genetics, Amino Acid Sequence : genetics
- in
- Genes, Chromosomes and Cancer
- volume
- 34
- issue
- 2
- pages
- 249 - 254
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- wos:000175101800012
- pmid:11979559
- scopus:0036259314
- pmid:11979559
- ISSN
- 1045-2257
- DOI
- 10.1002/gcc.10066
- language
- English
- LU publication?
- yes
- id
- 97fd84f2-e131-4044-99de-39009a48fa29 (old id 108411)
- alternative location
- http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11979559&dopt=Abstract
- date added to LUP
- 2016-04-01 11:54:44
- date last changed
- 2022-02-25 23:08:07
@article{97fd84f2-e131-4044-99de-39009a48fa29,
abstract = {{The t(11;20)(p15;q11) is a rare but recurrent translocation that so far has been described in only four acute myeloid leukemias (AMLs), two treatment-related myelodysplastic syndromes (t-MDSs), and one case of polycythemia vera. Recently, the t(11;20) was shown to result in a fusion of the NUP98 and TOP1 genes, with expression of the NUP98/TOP1 chimera encoded by the der(11)t(11;20), but not of the reciprocal TOP1/NUP98 on the der(20)t(11;20). The genomic breakpoints were subsequently mapped to introns 13 and 7 of NUP98 and TOP1, respectively. We present here a t-MDS with a three-way variant translocation, t(10;20;11)(q24;q11;p15), that generates a der(11)t(11;20) but not a der(20)t(11;20), strongly suggesting that the der(11) harbors the critical genetic rearrangement. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed a NUP98/TOP1 fusion in which exon 13 of NUP98 was fused in-frame with exon 8 of TOP1. Extra long (XL) genomic PCR and subsequent sequence analyses showed that the breakpoint in NUP98 occurred at nucleotide (nt) 3461 of intron 13, close to a MER (medium reiteration frequency interspersed repetitive element) repeat, and that the breakpoint in TOP1 was at nt 1436 of intron 7, downstream of a MIR (mammalian-wide interspersed repeats) repetitive element. Genomic XL PCR did not amplify the reciprocal TOP1/NUP98, nor was this chimera expressed, as expected from the cytogenetic finding. The present results provide further support for the involvement of the NUP98/TOP1 transcript, but not of the reciprocal one, in the development of MDS/AML. Furthermore, the three cases genomically characterized to date have all been treatment-related and have all harbored breakpoints in intron 13 of NUP98 and intron 7 of TOP1, suggesting that these introns are susceptible to chemotherapy-induced breakage.}},
author = {{Panagopoulos, Ioannis and Fioretos, Thoas and Isaksson, Margareth and Larsson, Gun and Billström, Rolf and Mitelman, Felix and Johansson, Bertil}},
issn = {{1045-2257}},
keywords = {{Chromosomes; Human; Pair 20 : genetics; DNA Topoisomerases; Type I : biosynthesis; Type I : genetics; Female; Middle Age; Molecular Sequence Data; Myelodysplastic Syndromes : chemically induced; Myelodysplastic Syndromes : genetics; Nuclear Pore Complex Proteins : biosynthesis; Neoplasm Proteins : genetics; Nuclear Pore Complex Proteins : genetics; Support; Non-U.S. Gov't; Translocation (Genetics) : genetics; Pair 11 : genetics; Pair 10 : genetics; Human : genetics; Case Report; Base Sequence : genetics; Amino Acid Sequence : genetics}},
language = {{eng}},
number = {{2}},
pages = {{249--254}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Genes, Chromosomes and Cancer}},
title = {{Expression of NUP98/TOP1, but not of TOP1/NUP98, in a treatment-related myelodysplastic syndrome with t(10;20;11)(q24;q11;p15).}},
url = {{http://dx.doi.org/10.1002/gcc.10066}},
doi = {{10.1002/gcc.10066}},
volume = {{34}},
year = {{2002}},
}