Identification of two critically deleted regions within chromosome segment 7q35-q36 in EVI1 deregulated myeloid leukemia cell lines

• Published in: PloS one Vol. 5; no. 1; p. e8676
• Main Authors: De Weer, An, Poppe, Bruce, Vergult, Sarah, Van Vlierberghe, Pieter, Petrick, Marjan, De Bock, Robrecht, Benoit, Yves, Noens, Lucien, De Paepe, Anne, Van Roy, Nadine, Menten, Björn, Speleman, Frank
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13.01.2010; Public Library of Science (PLoS)
• Subjects: Analysis; Apoptosis; Base Sequence; Biotechnology; Bone marrow; Cancer genetics; Cell Line, Tumor; Chromosome 7; Chromosome rearrangements; Chromosomes; Chromosomes, Human, Pair 7; CNTNAP2 gene; Cytogenetics; Deoxyribonucleic acid; Deregulation; DNA; DNA Primers; DNA-Binding Proteins - genetics; Genes; Genetics and Genomics/Cancer Genetics; Genomes; Hematology; Hematology/Acute Myeloid Leukemia; Humans; Hybridization; Hybridization analysis; Leukemia; Leukemia, Myeloid - genetics; Leukemia, Myeloid - pathology; MDS1 and EVI1 Complex Locus Protein; Monosomy; Mutation; Myeloid leukemia; Nucleic Acid Hybridization; Oncology/Hematological Malignancies; Patients; Phosphorylation; Prognosis; Proteins; Proto-Oncogenes - genetics; Sequence Deletion; Transcription Factors - genetics; Tumor cell lines; Tumor suppressor genes; Tumors; Belgium
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0008676

Chromosomal rearrangements involving the EVI1 proto-oncogene are a recurrent finding in myeloid leukemias and are indicative of a poor prognosis. Rearrangements of the EVI1 locus are often associated with monosomy 7 or cytogenetic detectable deletions of part of 7q. As EVI1 overexpression alone is not sufficient to induce leukemia, loss of a 7q tumour suppressor gene might be a required cooperating event. To test this hypothesis, we performed high-resolution array comparative genomic hybridization analysis of twelve EVI1 overexpressing patients and three EVI1 deregulated cell lines to search for 7q submicroscopic deletions. This analysis lead to the delineation of two critical regions, one of 0.39 Mb on 7q35 containing the CNTNAP2 gene and one of 1.33 Mb on chromosome bands 7q35-q36 comprising nine genes in EVI1 deregulated cell lines. These findings open the way to further studies aimed at identifying the culprit EVI1 implicated tumour suppressor genes on 7q.