title: A novel gene, ANKRD28 on 3p25, is fused with NUP98 on 11p15 in a cryptic 3-way translocation of t(3;5;11)(p25;q35;p15) in an adult patient with myelodysplastic syndrome/acute myelogenous leukemia.
abstract: We identified a novel gene fusion of ANKRD28 (ankyrin repeat domain 28) on 3p25 to NUP98 on 11p15 in a patient with adult myelodysplastic syndrome/acute myelogenous leukemia. A partially cryptic 3-way translocation, t(3;5;11)(p25;q35;p15), that had initially been supposed to be t(3;5)(p25;q35) was revealed by precise breakpoint mapping via fluorescence in situ hybridization analysis with bacterial artificial chromosome clones. This translocation produces the expression of 2 in-frame fusion transcripts, the novel ANKRD28-NUP98 and NUP98-NSD1, and 1 out-of-frame NSD1-ANKRD28 transcript. Transient overexpression of ANKRD28-NUP98 in NIH/3T3 cells, but not the C-terminal deletion mutant of ANKRD28 (DeltaC-ANKRD28), caused significantly increased focus formation compared with mock-transfectant controls. ANKRD28-NUP98 was localized in the nucleolus and cytoplasm, whereas ANKRD28 and DeltaC-ANKRD28 were found exclusively in the cytoplasm. Alteration of the subcellular localization of ANKRD28 might have contributed to the leukemogenesis in this case. This report is the first of ANKRD28 as an NUP98 fusion partner, and this case implies that this fusion may be responsible for hematologic malignancies.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Saitama Medical University, Saitama, Japan. miskw@saitama-med.ac.jp
authors.forename: Maho
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Fumiharu
authors.initials: F
authors.lastname: Yagasaki
authors.forename: Daisuke
authors.initials: D
authors.lastname: Okamura
authors.forename: Tomoya
authors.initials: T
authors.lastname: Maeda
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sugahara
authors.forename: Itsuro
authors.initials: I
authors.lastname: Jinnai
authors.forename: Masami
authors.initials: M
authors.lastname: Bessho
mesh_terms: D000328:Adult; D000818:Animals; D002466:Cell Nucleolus / Q000235:genetics / Q000378:metabolism; D002874:Chromosome Mapping; D022202:Chromosomes, Artificial, Bacterial; D002877:Chromosomes, Human / Q000235:genetics* / Q000378:metabolism; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D050939:Gene Fusion; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D051379:Mice; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000378:metabolism; D041681:NIH 3T3 Cells; D028861:Nuclear Pore Complex Proteins / Q000235:genetics* / Q000378:metabolism; D014178:Translocation, Genetic
chemical_list: C514564:ANKRD28 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D028861:Nuclear Pore Complex Proteins; C465451:Nup98 protein, human