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SHR Neuro Cancer Cardio Lipid Metab Microb

Nebral, K; Schmidt, HH; Haas, OA; Strehl, S.
NUP98 is fused to topoisomerase (DNA) IIbeta 180 kDa (TOP2B) in a patient with acute myeloid leukemia with a new t(3;11)(p24;p15).
Clin Cancer Res. 2005; 11(18):6489-6494 Doi: 10.1158/1078-0432.CCR-05-0150 (- Case Report) [OPEN ACCESS]
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Co-authors Med Uni Graz: Schmidt Helmut
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Abstract:: Purpose: The nucleoporin 98 kDa (NUP98) gene has been reported to be fused to 17 different partner genes in various hematologic malignancies with 11p15 aberrations. Cytogenetic analysis of an adult de novo acute myelogenous leukemia (M5a) revealed a t(3;11)(p24;p15), suggesting rearrangement of NUP98 with a novel partner gene. Experimental Design: Fluorescence in situ hybridization (FISH) was used to confirm the involvement of NUP98 in the t(3;11) (p24;p15). Selection of possible NUP98 partner genes was done by computer-aided analysis of the 3p24 region using the University of California Santa Cruz genome browser. Fusion gene-specific FISH and reverse transcription-PCR analyses were done to verify the presence of the new NUP98 fusion. Experimental Design: Fluorescence in situ hybridization (FISH) was used to confirm the involvement of NUP98 in the t(3;11) (p24;p15). Selection of possible NUP98 partner genes was done by computer-aided analysis of the 3p24 region using the University of California Santa Cruz genome browser. Fusion gene-specific FISH and reverse transcription-PCR analyses were done to verify the presence of the new NUP98 fusion. Results: FISH analysis using a NUP98-specific clone showed a split signal, indicating that the NUP98 gene was affected by the translocation. Of the genes localized at 3p24, TOP2B was selected as a possible fusion partner candidate gene. Dual-color fusion gene-specific FISH and reverse transcription-PCR analysis verified that NUP98 was indeed fused to TOP2B. In addition to reciprocal NUP98-TOP2B and TOP2B-NUP98 in-frame fusion transcripts, an alternatively spliced out-of-frame TOP2B-NUP98 transcript that resulted in a premature stop codon was detected. Analysis of the genomic breakpoints revealed typical signs of nonhomologous end joining resulting from error-prone DNA repair. Conclusions: TOP2B encodes a type 11 topoisomerase, which is involved in DNA transcription, replication, recombination, and mitosis, and besides TOP1, represents the second NUP98 fusion partner gene that belongs to the topoisomerase gene family.This finding emphasizes the important role of topoisomerases in malignant transformation processes.
Find related publications in this database (using NLM MeSH Indexing): Acute Disease -; Amino Acid Sequence -; Base Sequence -; Chromosomes, Human, Pair 11 - genetics; Chromosomes, Human, Pair 3 - genetics; DNA Topoisomerases, Type II - genetics; DNA-Binding Proteins - genetics; Humans -; In Situ Hybridization, Fluorescence -; Leukemia, Myeloid - genetics; Male -; Middle Aged -; Molecular Sequence Data -; Nuclear Pore Complex Proteins - genetics; Oncogene Proteins, Fusion - genetics; RNA, Neoplasm - genetics; Reverse Transcriptase Polymerase Chain Reaction -; Sequence Homology, Nucleic Acid -; Translocation, Genetic -