Source:http://linkedlifedata.com/resource/pubmed/id/11979559
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2002-5-23
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA Topoisomerases, Type I,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Pore Complex Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/nuclear pore complex protein 98
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1045-2257
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pubmed:author | |
pubmed:copyrightInfo |
Copyright 2002 Wiley-Liss, Inc.
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pubmed:issnType |
Print
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pubmed:volume |
34
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
249-54
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:11979559-Amino Acid Sequence,
pubmed-meshheading:11979559-Base Sequence,
pubmed-meshheading:11979559-Chromosomes, Human,
pubmed-meshheading:11979559-Chromosomes, Human, Pair 10,
pubmed-meshheading:11979559-Chromosomes, Human, Pair 11,
pubmed-meshheading:11979559-Chromosomes, Human, Pair 20,
pubmed-meshheading:11979559-DNA Topoisomerases, Type I,
pubmed-meshheading:11979559-Female,
pubmed-meshheading:11979559-Humans,
pubmed-meshheading:11979559-Middle Aged,
pubmed-meshheading:11979559-Molecular Sequence Data,
pubmed-meshheading:11979559-Myelodysplastic Syndromes,
pubmed-meshheading:11979559-Neoplasm Proteins,
pubmed-meshheading:11979559-Nuclear Pore Complex Proteins,
pubmed-meshheading:11979559-Translocation, Genetic
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pubmed:year |
2002
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pubmed:articleTitle |
Expression of NUP98/TOP1, but not of TOP1/NUP98, in a treatment-related myelodysplastic syndrome with t(10;20;11)(q24;q11;p15).
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pubmed:affiliation |
Department of Clinical Genetics, University Hospital, Lund, Sweden. ioannis.panagopoulos@klingen.lu.se
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pubmed:publicationType |
Journal Article,
Case Reports,
Research Support, Non-U.S. Gov't
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