title: Complex chromosomal rearrangements leading to MECOM overexpression are recurrent in myeloid malignancies with various 3q abnormalities.
abstract: Chromosomal rearrangements involving 3q26 are recurrent findings in myeloid malignancies leading to MECOM overexpression, which has been associated with a very poor prognosis. Other 3q abnormalities have been reported and cryptic MECOM rearrangements have been identified in some cases. By fluorescence in situ hybridization (FISH) analysis, we investigated 97 acute myeloid leukemia/myelodysplastic syndrome patients with various 3q abnormalities to determine the role and the frequency of the involvement of MECOM. We identified MECOM rearrangements in 51 patients, most of them showed 3q26 involvement by chromosome banding analysis (CBA): inv(3)/t(3;3) (n = 26) and other balanced 3q26 translocations (t(3q26)) (n = 15); the remaining cases (n = 10) showed various 3q abnormalities: five with balanced translocations involving 3q21 or 3q25; two with homogenously staining region (hsr) on 3q; and three with other various 3q abnormalities. Complex rearrangements with multiple breakpoints on 3q, masking 3q26 involvement, were identified in cases with 3q21/3q25 translocations. Furthermore, multiple breaks were observed in two cases with t(3q26), suggesting that complex rearrangement may also occur in apparently simple t(3q26). Intrachromosomal gene amplification was another mechanism leading to MECOM overexpression in two cases with hsr on 3q. In the last three cases, FISH analysis revealed 3q26 involvement that was missed by CBA because of metaphases' suboptimal quality. All cases with MECOM rearrangements showed overexpression by real-time quantitative PCR. Finally, MECOM rearrangements can occur in patients with 3q abnormalities even in the absence of specific 3q26 involvement, underlining that their frequency is underestimated. As MECOM rearrangement has been associated with very poor prognosis, its screening should be performed in patients with any 3q abnormalities.
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology and Medical Oncology "Seragnoli," Sant'Orsola-Malpighi Hospital-University, Bologna, Italy.
authors.forename: Carmen
authors.initials: C
authors.lastname: Baldazzi
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology and Medical Oncology "Seragnoli," Sant'Orsola-Malpighi Hospital-University, Bologna, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Luatti
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology and Medical Oncology "Seragnoli," Sant'Orsola-Malpighi Hospital-University, Bologna, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Zuffa
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology and Medical Oncology "Seragnoli," Sant'Orsola-Malpighi Hospital-University, Bologna, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Papayannidis
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology and Medical Oncology "Seragnoli," Sant'Orsola-Malpighi Hospital-University, Bologna, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Ottaviani
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology and Medical Oncology "Seragnoli," Sant'Orsola-Malpighi Hospital-University, Bologna, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Marzocchi
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology and Medical Oncology "Seragnoli," Sant'Orsola-Malpighi Hospital-University, Bologna, Italy.
authors.forename: Gaia
authors.initials: G
authors.lastname: Ameli
authors.affiliation: Department of Medical Sciences, University of Ferrara-Arcispedale Sant'Anna, Ferrara, Italy.
authors.forename: Maria Antonella
authors.initials: MA
authors.lastname: Bardi
authors.affiliation: Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Bonaldi
authors.affiliation: Department of General Medicine, UOSD Hematology, Santa Maria Della Misericordia Hospital, Rovigo, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Paolini
authors.affiliation: Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Gurrieri
authors.affiliation: Department of Medical Sciences, University of Ferrara-Arcispedale Sant'Anna, Ferrara, Italy.
authors.forename: Gian Matteo
authors.initials: GM
authors.lastname: Rigolin
authors.affiliation: Department of Medical Sciences, University of Ferrara-Arcispedale Sant'Anna, Ferrara, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cuneo
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology and Medical Oncology "Seragnoli," Sant'Orsola-Malpighi Hospital-University, Bologna, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology and Medical Oncology "Seragnoli," Sant'Orsola-Malpighi Hospital-University, Bologna, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Cavo
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology and Medical Oncology "Seragnoli," Sant'Orsola-Malpighi Hospital-University, Bologna, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Testoni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002871:Chromosome Banding; D002893:Chromosomes, Human, Pair 3; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D000074008:MDS1 and EVI1 Complex Locus Protein; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D011519:Proto-Oncogenes / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; D014157:Transcription Factors