PMID- 16166424
OWN - NLM
STAT- MEDLINE
DCOM- 20051108
LR  - 20171116
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 11
IP  - 18
DP  - 2005 Sep 15
TI  - 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).
PG  - 6489-94
AB  - 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. 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 II 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.
FAU - Nebral, Karin
AU  - Nebral K
AD  - Children's Cancer Research Institute, Vienna, Austria.
FAU - Schmidt, Helmut H
AU  - Schmidt HH
FAU - Haas, Oskar A
AU  - Haas OA
FAU - Strehl, Sabine
AU  - Strehl S
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Nuclear Pore Complex Proteins)
RN  - 0 (Nup98 protein, human)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (Poly-ADP-Ribose Binding Proteins)
RN  - 0 (RNA, Neoplasm)
RN  - EC 5.99.1.3 (DNA Topoisomerases, Type II)
RN  - EC 5.99.1.3 (TOP2B protein, human)
SB  - IM
MH  - Acute Disease
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Chromosomes, Human, Pair 11/genetics
MH  - Chromosomes, Human, Pair 3/genetics
MH  - DNA Topoisomerases, Type II/*genetics
MH  - DNA-Binding Proteins/*genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Leukemia, Myeloid/*genetics
MH  - Male
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Nuclear Pore Complex Proteins/*genetics
MH  - Oncogene Proteins, Fusion/*genetics
MH  - Poly-ADP-Ribose Binding Proteins
MH  - RNA, Neoplasm/genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sequence Homology, Nucleic Acid
MH  - *Translocation, Genetic
EDAT- 2005/09/17 09:00
MHDA- 2005/11/09 09:00
CRDT- 2005/09/17 09:00
PHST- 2005/09/17 09:00 [pubmed]
PHST- 2005/11/09 09:00 [medline]
PHST- 2005/09/17 09:00 [entrez]
AID - 11/18/6489 [pii]
AID - 10.1158/1078-0432.CCR-05-0150 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2005 Sep 15;11(18):6489-94. doi: 10.1158/1078-0432.CCR-05-0150.