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Fusion of the NUP98 gene and the homeobox gene HOXC13 in acute myeloid leukemia with t(11;12)(p15;q13)
Author(s) -
Panagopoulos Ioannis,
Isaksson Margareth,
Billström Rolf,
Strömbeck Bodil,
Mitelman Felix,
Johansson Bertil
Publication year - 2003
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.10139
Subject(s) - fusion gene , myeloid leukemia , exon , homeobox , biology , homeobox a1 , gene , microbiology and biotechnology , cancer research , chromosomal translocation , fusion protein , runx1t1 , myeloid , genetics , transcription factor , recombinant dna
The NUP98 gene at 11p15 is known to be fused to DDX10, HOXA9, HOXA11, HOXA13, HOXD11, HOXD13, LEDGF , NSD1, NSD3, PMX1 , RAP1GDS1 , and TOP1 in various hematologic malignancies. The common theme in all NUP98 chimeras is a transcript consisting of the 5′ part of NUP98 and the 3′ portion of the partner gene; however, apart from the frequent fusion to different homeobox genes, there is no apparent similarity among the other partners. We here report a de novo acute myeloid leukemia with a t(11;12)(p15;q13), resulting in a novel NUP98/HOXC13 fusion. Fluorescence in situ hybridization analyses, by the use of probes covering NUP98 and the HOXC gene cluster at 12q13, revealed a fusion signal at the der(11)t(11;12), indicating a NUP98/HOXC chimera, whereas no fusion was found on the der(12)t(11;12), suggesting that the translocation was accompanied by a deletion of the reciprocal fusion gene. Reverse transcription‐PCR and sequence analyses showed that exon 16 (nucleotide 2290) of NUP98 was fused in‐frame with exon 2 (nucleotide 852) of HOXC13 . Neither the HOXC13/NUP98 transcript nor the normal HOXC13 was expressed. The present results, together with previous studies of NUP98/ homeobox gene fusions, strongly indicate that NUP98/HOXC13 is of pathogenetic importance in t(11;12)‐positive acute myeloid leukemia. © 2002 Wiley‐Liss, Inc.