title: Fusion of the NUP98 gene and the homeobox gene HOXC13 in acute myeloid leukemia with t(11;12)(p15;q13).
abstract: 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.
authors.affiliation: Department of Clinical Genetics, Lund University Hospital, Sweden. ioannis.panagopoulos@klingen.lu.se
authors.forename: Ioannis
authors.initials: I
authors.lastname: Panagopoulos
authors.forename: Margareth
authors.initials: M
authors.lastname: Isaksson
authors.forename: Rolf
authors.initials: R
authors.lastname: Billström
authors.forename: Bodil
authors.initials: B
authors.lastname: Strömbeck
authors.forename: Felix
authors.initials: F
authors.lastname: Mitelman
authors.forename: Bertil
authors.initials: B
authors.lastname: Johansson
mesh_terms: D000208:Acute Disease; D000595:Amino Acid Sequence; D001483:Base Sequence; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D008969:Molecular Sequence Data; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: C410305:HOXC13 protein, human; D018398:Homeodomain Proteins; C470262:NUP98-HOXC13 fusion protein, human; D028861:Nuclear Pore Complex Proteins; C465451:Nup98 protein, human; D015514:Oncogene Proteins, Fusion