title: Conventional cytogenetics and breakpoint distribution by fluorescent in situ hybridization in patients with malignant hemopathies associated with inv(3)(q21;q26) and t(3;3)(q21;q26).
abstract: Inv(3)(q21q26)/t(3;3)(q21;q26) is recognized as a distinctive entity of acute myeloid leukemia (AML) with recurrent genetic abnormalities of prognostic significance. It occurs in 1-2.5% of AML and is also observed in myelodysplastic syndromes and in the blastic phase of chronic myeloid leukemia. The molecular consequence of the inv(3)/t(3;3) rearrangements is the juxtaposition of the ribophorin I (RPN1) gene (located in band 3q21) with the ecotropic viral integration site 1 (EVI1) gene (located in band 3q26.2). Following conventional cytogenetics to determine the karyotype, fluorescent in situ hybridization (FISH) with a panel of bacterial artificial chromosome clones was used to map the breakpoints involved in 15 inv(3)/t(3;3). Inv(3) or t(3;3) was the sole karyotypic anomaly in 6 patients, while additional abnormalities were identified in the remaining 9 patients, including 4 with monosomy of chromosome7 (-7) or a deletion of its long arm (7q-). Breakpoints in band 3q21 were distributed in a 235 kb region centromeric to and including the RPN1 locus, while those in band 3q26.2 were scattered in a 900 kb region located on each side of and including the EVI1 locus. In contrast to most of the inversions and translocations associated with AML that lead to fusion genes, inv(3)/t(3;3) does not generate a chimeric gene, but rather induces gene overexpression. The wide dispersion of the breakpoints in bands 3q21 and 3q26 and the heterogeneity of the genomic consequences could explain why the mechanisms leading to leukemogenesis are still poorly understood. Therefore, it is important to further characterize these chromosomal abnormalities by FISH.
authors.affiliation: University of Brest, Faculty of Medicine and Health Sciences, Brest, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: De Braekeleer
authors.forename: Nathalie
authors.initials: N
authors.lastname: Douet-Guilbert
authors.forename: Audrey
authors.initials: A
authors.lastname: Basinko
authors.forename: Clément
authors.initials: C
authors.lastname: Bovo
authors.forename: Nadia
authors.initials: N
authors.lastname: Guéganic
authors.forename: Marie-Josée
authors.initials: MJ
authors.lastname: Le Bris
authors.forename: Frédéric
authors.initials: F
authors.lastname: Morel
authors.forename: Marc
authors.initials: M
authors.lastname: De Braekeleer
mesh_terms: D019457:Chromosome Breakage; D007446:Chromosome Inversion / Q000235:genetics*; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D003582:Cytogenetics / Q000379:methods*; D015342:DNA Probes / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D019337:Hematologic Neoplasms / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D000074008:MDS1 and EVI1 Complex Locus Protein; D008297:Male; D008875:Middle Aged; D011519:Proto-Oncogenes / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: D015342:DNA Probes; D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; D014157:Transcription Factors