Identification ofNUP98abnormalities in acute leukemia:JARID1A(12p13) as a new partner gene

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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 isNUP98(11p15). AsNUP98is close to the 11p telomere, small translocations might easily be missed. Using aNUP98-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. NeitherNUP98translocations nor deletions were identified in cases with normal karyotypes, indicating these aberrations may be very rare in this group. However,NUP98deletions were observed in four cases with unbalanced 11p aberrations, indicating that the breakpoint is centromeric ofNUP98. Rearrangements ofNUP98were identified in two patients, both showing 11p abnormalities in the diagnostic karyotype: a t(4;11)(q1?3;p15) with expression of theNUP98–RAP1GDS1fusion 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.JARID1Awas identified as the fusion partner ofNUP98using 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 ofJARID1Aas a partner gene in leukemia. © 2006 Wiley-Liss, Inc.

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