Biomaterial Database

Complex chromosomal rearrangements leading to MECOM overexpression are recurrent in myeloid malignancies with various 3q abnormalities. 2016

Carmen Baldazzi, and Simona Luatti, and Elisa Zuffa, and Cristina Papayannidis, and Emanuela Ottaviani, and Giulia Marzocchi, and Gaia Ameli, and Maria Antonella Bardi, and Laura Bonaldi, and Rossella Paolini, and Carmela Gurrieri, and Gian Matteo Rigolin, and Antonio Cuneo, and Giovanni Martinelli, and Michele Cavo, and Nicoletta Testoni

Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology and Medical Oncology "Seragnoli," Sant'Orsola-Malpighi Hospital-University, Bologna, Italy.

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.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D009190	Myelodysplastic Syndromes	Clonal hematopoietic stem cell disorders characterized by dysplasia in one or more hematopoietic cell lineages. They predominantly affect patients over 60, are considered preleukemic conditions, and have high probability of transformation into ACUTE MYELOID LEUKEMIA.	Dysmyelopoietic Syndromes,Hematopoetic Myelodysplasia,Dysmyelopoietic Syndrome,Hematopoetic Myelodysplasias,Myelodysplasia, Hematopoetic,Myelodysplasias, Hematopoetic,Myelodysplastic Syndrome,Syndrome, Dysmyelopoietic,Syndrome, Myelodysplastic,Syndromes, Dysmyelopoietic,Syndromes, Myelodysplastic
D011519	Proto-Oncogenes	Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Proto-oncogenes have names of the form c-onc.	Proto-Oncogene,Proto Oncogene,Proto Oncogenes
D002871	Chromosome Banding	Staining of bands, or chromosome segments, allowing the precise identification of individual chromosomes or parts of chromosomes. Applications include the determination of chromosome rearrangements in malformation syndromes and cancer, the chemistry of chromosome segments, chromosome changes during evolution, and, in conjunction with cell hybridization studies, chromosome mapping.	Banding, Chromosome,Bandings, Chromosome,Chromosome Bandings
D002893	Chromosomes, Human, Pair 3	A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification.	Chromosome 3
D004268	DNA-Binding Proteins	Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.	DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000074008	MDS1 and EVI1 Complex Locus Protein	A DNA binding protein, transcriptional regulator, and proto-oncogene protein that contains 10 CYS2-HIS2 ZINC FINGERS. It functions as a positive or negative regulator of expression for target genes involved in organism development.	Ecotropic Virus Integration Site 1 Protein Homolog,MECOM Protein,Myelodysplasia Syndrome-Associated Protein 1,Zinc Finger Protein Evi1,Myelodysplasia Syndrome Associated Protein 1