PMID- 15951287
OWN - NLM
STAT- MEDLINE
DCOM- 20060810
LR  - 20091119
IS  - 1592-8721 (Electronic)
IS  - 0390-6078 (Linking)
VI  - 90
IP  - 6
DP  - 2005 Jun
TI  - Screening for NUP98 rearrangements in hematopoietic malignancies by fluorescence 
      in situ hybridization.
PG  - 746-52
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to determine the incidence 
      of rearrangements of NUP98 (the gene coding for nucleoporin 98kDa protein) in 
      childhood acute myeloid leukemia (AML) and selected patients with 11p13-15 
      rearrangements. This aim was achieved using a fluorescence in situ hybridization 
      (FISH) assay that allows the detection of NUP98 aberrations independently of the 
      partner gene involved. DESIGN AND METHODS: Screening of 59 consecutive patients 
      enrolled in the Austrian AML-BFM93 clinical trial was performed by dual-color 
      FISH. In addition, 14 selected cases with various hematologic malignancies and 
      11p13-15 aberrations were analyzed. NUP98-positive cases were further 
      investigated by fusion gene-specific FISH and reverse transcription polymerase 
      chain reaction assays. RESULTS: Among the 59 AML patients, one NUP98-NSD1 
      positive case (1.7%) was detected. Among the 14 selected patients, five new NUP98 
      positive cases were determined. Two cases showed an inv(11)(p15q22)/NUP98-DDX10 
      fusion, one each displayed a t(5;11)(q35;p15)/NUP98-NSD1 and a 
      t(11;20)(p15;q12)/NUP98-TOP1 fusion, and one case with a putative new fusion 
      partner gene at 3p24 was identified. INTERPRETATION AND CONCLUSIONS: The observed 
      frequency of 1.7% confirmed the low incidence of NUP98 rearrangements in 
      childhood AML. The low occurrence of NUP98 rearrangements in selected samples 
      with 11p13-15 alterations suggests the existence of variable chromosomal 
      breakpoints and affected genes in this region. The identification of a new NUP98 
      fusion partner region confirms the evident promiscuity of NUP98. Thus, analysis 
      of NUP98 aberrations by FISH seems to be the method of choice for determining the 
      presence of these genetic lesions in unselected patients, and to confirm the 
      involvement of NUP98 in cases with 11p15 aberrations.
FAU - Nebral, Karin
AU  - Nebral K
AD  - Children's Cancer Research Institute, Vienna, Austria.
FAU - Konig, Margit
AU  - Konig M
FAU - Schmidt, Helmut H
AU  - Schmidt HH
FAU - Lutz, Dieter
AU  - Lutz D
FAU - Sperr, Wolfgang R
AU  - Sperr WR
FAU - Kalwak, Krzysztof
AU  - Kalwak K
FAU - Brugger, Stefan
AU  - Brugger S
FAU - Dworzak, Michael N
AU  - Dworzak MN
FAU - Haas, Oskar A
AU  - Haas OA
FAU - Strehl, Sabine
AU  - Strehl S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Italy
TA  - Haematologica
JT  - Haematologica
JID - 0417435
RN  - 0 (Nuclear Pore Complex Proteins)
RN  - 0 (nuclear pore complex protein 98)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Child
MH  - Child, Preschool
MH  - *Chromosome Aberrations
MH  - Chromosome Inversion
MH  - Female
MH  - Hematologic Neoplasms/*diagnosis/*genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Leukemia, Myeloid, Acute/*diagnosis/*genetics
MH  - Male
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Nuclear Pore Complex Proteins/*biosynthesis
MH  - Translocation, Genetic
EDAT- 2005/06/14 09:00
MHDA- 2006/08/11 09:00
CRDT- 2005/06/14 09:00
PHST- 2005/06/14 09:00 [pubmed]
PHST- 2006/08/11 09:00 [medline]
PHST- 2005/06/14 09:00 [entrez]
PST - ppublish
SO  - Haematologica. 2005 Jun;90(6):746-52.