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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)
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published
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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
external identifiers
  • wos:000175101800012
  • pmid:11979559
  • scopus:0036259314
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
2007-07-09 09:01:13
date last changed
2017-04-16 03:30:26
@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},
  keyword      = {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},
  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},
  volume       = {34},
  year         = {2002},
}