title: Identification of NUP98 abnormalities in acute leukemia: JARID1A (12p13) as a new partner gene.
abstract: Chromosome rearrangements are found in many acute leukemias. As a result, genes at the breakpoints can be disrupted, forming fusion genes. One of the genes involved in several chromosome aberrations in hematological malignancies is NUP98 (11p15). As NUP98 is close to the 11p telomere, small translocations might easily be missed. Using a NUP98-specific split-signal fluorescence in situ hybridization (FISH) probe combination, we analyzed 84 patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia, or myelodysplastic syndrome with either normal karyotypes or 11p abnormalities to investigate whether there are unidentified 11p15 rearrangements. Neither NUP98 translocations nor deletions were identified in cases with normal karyotypes, indicating these aberrations may be very rare in this group. However, NUP98 deletions were observed in four cases with unbalanced 11p aberrations, indicating that the breakpoint is centromeric of NUP98. Rearrangements of NUP98 were identified in two patients, both showing 11p abnormalities in the diagnostic karyotype: a t(4;11)(q1?3;p15) with expression of the NUP98-RAP1GDS1 fusion product detected in a 60-year-old woman with AML-M0, and an add(11)(p15) with a der(21)t(11;21)(p15;p13) observed cytogenetically in a 1-year-old boy with AML-M7. JARID1A was identified as the fusion partner of NUP98 using 3' RACE, RT-PCR, and FISH. JARID1A, at 12p13, codes for retinoblastoma binding protein 2, a protein implicated in transcriptional regulation. This is the first report of JARID1A as a partner gene in leukemia.
authors.affiliation: Department of Genetics, Centre for Biomedical Genetics, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Laura J C M
authors.initials: LJ
authors.lastname: van Zutven
authors.forename: Emine
authors.initials: E
authors.lastname: Onen
authors.forename: Sandra C J M
authors.initials: SC
authors.lastname: Velthuizen
authors.forename: Ellen
authors.initials: E
authors.lastname: van Drunen
authors.forename: Anne R M
authors.initials: AR
authors.lastname: von Bergh
authors.forename: Marry M
authors.initials: MM
authors.lastname: van den Heuvel-Eibrink
authors.forename: Angelo
authors.initials: A
authors.lastname: Veronese
authors.forename: Cristina
authors.initials: C
authors.lastname: Mecucci
authors.forename: Massimo
authors.initials: M
authors.lastname: Negrini
authors.forename: Georgine E
authors.initials: GE
authors.lastname: de Greef
authors.forename: H Berna
authors.initials: HB
authors.lastname: Beverloo
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002881:Chromosomes, Human, Pair 12; D017931:DNA Primers; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007621:Karyotyping; D007938:Leukemia / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*
chemical_list: D017931:DNA Primers; D028861:Nuclear Pore Complex Proteins; C465451:Nup98 protein, human