PMID- 26815134 OWN - NLM STAT- MEDLINE DCOM- 20160926 LR - 20171116 IS - 1098-2264 (Electronic) IS - 1045-2257 (Linking) VI - 55 IP - 4 DP - 2016 Apr TI - Complex chromosomal rearrangements leading to MECOM overexpression are recurrent in myeloid malignancies with various 3q abnormalities. PG - 375-88 LID - 10.1002/gcc.22341 [doi] AB - 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. CI - (c) 2016 Wiley Periodicals, Inc. FAU - Baldazzi, Carmen AU - Baldazzi C AD - Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology and Medical Oncology "Seragnoli," Sant'Orsola-Malpighi Hospital-University, Bologna, Italy. FAU - Luatti, Simona AU - Luatti S AD - Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology and Medical Oncology "Seragnoli," Sant'Orsola-Malpighi Hospital-University, Bologna, Italy. FAU - Zuffa, Elisa AU - Zuffa E AD - Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology and Medical Oncology "Seragnoli," Sant'Orsola-Malpighi Hospital-University, Bologna, Italy. FAU - Papayannidis, Cristina AU - Papayannidis C AD - Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology and Medical Oncology "Seragnoli," Sant'Orsola-Malpighi Hospital-University, Bologna, Italy. FAU - Ottaviani, Emanuela AU - Ottaviani E AD - Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology and Medical Oncology "Seragnoli," Sant'Orsola-Malpighi Hospital-University, Bologna, Italy. FAU - Marzocchi, Giulia AU - Marzocchi G AD - Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology and Medical Oncology "Seragnoli," Sant'Orsola-Malpighi Hospital-University, Bologna, Italy. FAU - Ameli, Gaia AU - Ameli G AD - Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology and Medical Oncology "Seragnoli," Sant'Orsola-Malpighi Hospital-University, Bologna, Italy. FAU - Bardi, Maria Antonella AU - Bardi MA AD - Department of Medical Sciences, University of Ferrara-Arcispedale Sant'Anna, Ferrara, Italy. FAU - Bonaldi, Laura AU - Bonaldi L AD - Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy. FAU - Paolini, Rossella AU - Paolini R AD - Department of General Medicine, UOSD Hematology, Santa Maria Della Misericordia Hospital, Rovigo, Italy. FAU - Gurrieri, Carmela AU - Gurrieri C AD - Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy. FAU - Rigolin, Gian Matteo AU - Rigolin GM AD - Department of Medical Sciences, University of Ferrara-Arcispedale Sant'Anna, Ferrara, Italy. FAU - Cuneo, Antonio AU - Cuneo A AD - Department of Medical Sciences, University of Ferrara-Arcispedale Sant'Anna, Ferrara, Italy. FAU - Martinelli, Giovanni AU - Martinelli G AD - Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology and Medical Oncology "Seragnoli," Sant'Orsola-Malpighi Hospital-University, Bologna, Italy. FAU - Cavo, Michele AU - Cavo M AD - Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology and Medical Oncology "Seragnoli," Sant'Orsola-Malpighi Hospital-University, Bologna, Italy. FAU - Testoni, Nicoletta AU - Testoni N AD - Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology and Medical Oncology "Seragnoli," Sant'Orsola-Malpighi Hospital-University, Bologna, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160127 PL - United States TA - Genes Chromosomes Cancer JT - Genes, chromosomes & cancer JID - 9007329 RN - 0 (DNA-Binding Proteins) RN - 0 (MDS1 and EVI1 Complex Locus Protein) RN - 0 (MECOM protein, human) RN - 0 (Transcription Factors) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Chromosome Banding MH - *Chromosomes, Human, Pair 3 MH - DNA-Binding Proteins/*genetics MH - Female MH - *Gene Expression Regulation, Neoplastic MH - Humans MH - In Situ Hybridization, Fluorescence MH - Leukemia, Myeloid, Acute/*genetics MH - MDS1 and EVI1 Complex Locus Protein MH - Male MH - Middle Aged MH - Myelodysplastic Syndromes/*genetics MH - Proto-Oncogenes/*genetics MH - Real-Time Polymerase Chain Reaction MH - Transcription Factors/*genetics MH - *Translocation, Genetic EDAT- 2016/01/28 06:00 MHDA- 2016/09/27 06:00 CRDT- 2016/01/28 06:00 PHST- 2015/10/14 00:00 [received] PHST- 2015/11/25 00:00 [revised] PHST- 2015/12/03 00:00 [accepted] PHST- 2016/01/28 06:00 [entrez] PHST- 2016/01/28 06:00 [pubmed] PHST- 2016/09/27 06:00 [medline] AID - 10.1002/gcc.22341 [doi] PST - ppublish SO - Genes Chromosomes Cancer. 2016 Apr;55(4):375-88. doi: 10.1002/gcc.22341. Epub 2016 Jan 27.