NUP98-HOXD13 gene fusion in therapy-related acute myelogenous leukemia.
A novel chromosomal translocation, t(2;11)(q31;p15), was identified in a patient with therapy-related acute myelogenous leukemia (t-AML). Fluorescence in situ hybridization experiments mapped the breakpoint near NUP98; Southern blot analysis demonstrated that the nucleoporin gene NUP98 was disrupted by this translocation. We used rapid amplification of cDNA ends to identify a chimeric mRNA. An in-frame, chimeric mRNA that fused NUP98 sequences to the homeobox gene HOXD13 was cloned; the predicted fusion protein contains both the GLFG repeats from NUP98 as well as the homeodomain from HOXD13. The NUP98-HOXD13 fusion is structurally similar to the NUP98-HOXA9 fusion previously identified in patients with AML, leading to the speculation that NUP98-homeobox gene fusions may be oncogenic. Moreover, this report, along with a recent study that demonstrated NUP98-DDX10 fusions in patients with t-AML, raises the possibility that NUP98 may be a previously unsuspected target for chromosomal translocations in patients with t-AML.
Raza-Egilmez
S Z
SZ
Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Jani-Sait
S N
SN
Grossi
M
M
Higgins
M J
MJ
Shows
T B
TB
Aplan
P D
PD
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D019677:Artificial Gene Fusion; D001854:Bone Marrow Cells / Q000473:pathology; D002648:Child; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D002889:Chromosomes, Human, Pair 2; D015321:Gene Rearrangement; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced* / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D016609:Neoplasms, Second Primary / Q000139:chemically induced / Q000235:genetics; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014157:Transcription Factors; D014178:Translocation, Genetic
C513184:HOXD13 protein, human; D018398:Homeodomain Proteins; D008565:Membrane Proteins; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C093350:nuclear pore complex protein 98