title: Screening for NUP98 rearrangements in hematopoietic malignancies by fluorescence in situ hybridization.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  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.
authors.affiliation: Children's Cancer Research Institute, Vienna, Austria.
authors.forename: Karin
authors.initials: K
authors.lastname: Nebral
authors.forename: Margit
authors.initials: M
authors.lastname: König
authors.forename: Helmut H
authors.initials: HH
authors.lastname: Schmidt
authors.forename: Dieter
authors.initials: D
authors.lastname: Lutz
authors.forename: Wolfgang R
authors.initials: WR
authors.lastname: Sperr
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kalwak
authors.forename: Stefan
authors.initials: S
authors.lastname: Brugger
authors.forename: Michael N
authors.initials: MN
authors.lastname: Dworzak
authors.forename: Oskar A
authors.initials: OA
authors.lastname: Haas
authors.forename: Sabine
authors.initials: S
authors.lastname: Strehl
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D007446:Chromosome Inversion; D005260:Female; D019337:Hematologic Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D028861:Nuclear Pore Complex Proteins / Q000096:biosynthesis*; D014178:Translocation, Genetic
chemical_list: D028861:Nuclear Pore Complex Proteins; C093350:nuclear pore complex protein 98