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Identification of NUP98 abnormalities in acute leukemia: JARID1A (12p13) as a new partner gene
Author(s) -
van Zutven Laura J. C. M.,
Önen Emine,
Velthuizen Sandra C. J. M.,
van Drunen Ellen,
von Bergh Anne R. M.,
van den HeuvelEibrink Marry M.,
Veronese Angelo,
Mecucci Cristina,
Negrini Massimo,
de Greef Georgine E.,
Beverloo H. Berna
Publication year - 2006
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20308
Subject(s) - identification (biology) , leukemia , gene , medicine , genetics , acute leukemia , computational biology , biology , botany
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. © 2006 Wiley‐Liss, Inc.