title: EVI1 overexpression in t(3;17) positive myeloid malignancies results from juxtaposition of EVI1 to the MSI2 locus at 17q22.
abstract: Chromosomal translocations involving the EVI1 locus are a recurrent finding in myeloid leukemia and are associated with poor prognosis. In this study, we performed a detailed molecular characterization of the recurrent translocation t(3;17)(q26;q22) in 13 hematologic malignancies. The EVI1 gene locus was rearranged in all 13 patients and was associated with EVI1 overexpression. In 9 out of 13 patients, the 17q breakpoints clustered in a 250 kb region on band 17q22 encompassing the MSI2 (musashi homologue 2) gene. Expression analyses failed to demonstrate ectopic MSI2 expression or the presence of an MSI2/EVI1 fusion gene. In conclusion, we show for the first time that the t(3;17) is indeed a recurrent chromosomal aberration in myeloid malignancies. In keeping with findings in other recurrent 3q26 rearrangements, overexpression of the EVI1 gene appears to be the major contributor to leukemogenesis in patients with a t(3;17).
authors.affiliation: Centre for Medical Genetics Gent, Ghent University Hospital, Ghent, Belgium.
authors.forename: An
authors.initials: A
authors.lastname: De Weer
authors.forename: Frank
authors.initials: F
authors.lastname: Speleman
authors.forename: Barbara
authors.initials: B
authors.lastname: Cauwelier
authors.forename: Nadine
authors.initials: N
authors.lastname: Van Roy
authors.forename: Nurten
authors.initials: N
authors.lastname: Yigit
authors.forename: Bruno
authors.initials: B
authors.lastname: Verhasselt
authors.forename: Barbara
authors.initials: B
authors.lastname: De Moerloose
authors.forename: Yves
authors.initials: Y
authors.lastname: Benoit
authors.forename: Lucien
authors.initials: L
authors.lastname: Noens
authors.forename: Dominik
authors.initials: D
authors.lastname: Selleslag
authors.forename: Eric
authors.initials: E
authors.lastname: Lippert
authors.forename: Stephanie
authors.initials: S
authors.lastname: Struski
authors.forename: Christian
authors.initials: C
authors.lastname: Bastard
authors.forename: Anne
authors.initials: A
authors.lastname: De Paepe
authors.forename: Peter
authors.initials: P
authors.lastname: Vandenberghe
authors.forename: Anne
authors.initials: A
authors.lastname: Hagemeijer
authors.forename: Nicole
authors.initials: N
authors.lastname: Dastugue
authors.forename: Bruce
authors.initials: B
authors.lastname: Poppe
mesh_terms: D002886:Chromosomes, Human, Pair 17; D002893:Chromosomes, Human, Pair 3; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D006801:Humans; D000074008:MDS1 and EVI1 Complex Locus Protein; D009196:Myeloproliferative Disorders / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011519:Proto-Oncogenes / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; C438151:MSI2 protein, human; D015514:Oncogene Proteins, Fusion; D016601:RNA-Binding Proteins; D014157:Transcription Factors