Research Article: Identification of Two Critically Deleted Regions within Chromosome Segment 7q35-q36 in EVI1 Deregulated Myeloid Leukemia Cell Lines

Date Published: January 13, 2010

Publisher: Public Library of Science

Author(s): An De Weer, Bruce Poppe, Sarah Vergult, Pieter Van Vlierberghe, Marjan Petrick, Robrecht De Bock, Yves Benoit, Lucien Noens, Anne De Paepe, Nadine Van Roy, Björn Menten, Frank Speleman, Anita Brandstaetter.

Abstract: 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.

Partial Text: Chromosomal rearrangements involving chromosome band 3q26, such as translocations with various partner chromosomes or inversions of chromosome 3 are a recurrent finding in myeloid leukemias [1]. These aberrations contribute to the ectopic expression of the EVI1 proto-oncogene. EVI1 transcriptional activation has been reported in up to 10% of myeloid leukemia patients, even in the absence of 3q26 rearrangements, and is an independent indicator of adverse prognosis [2].

Based on karyotyping and FISH analysis, two critical regions, one on chromosome band 7q22 [14] and one on chromosome bands 7q32–q35 [15], have been identified as the targets for 7q deletions in myeloid leukemia. In this study, array CGH was applied to search for deletions on chromosome 7 at ultra-high resolution. Using this approach, we identified several submicroscopic 7p and 7q deletions in EVI1 overexpressing patients and cell lines (Table 3 and Figure 1) including two critically deleted regions on 7q35–q36 in EVI1 deregulated cell lines. These deletions were confirmed using FISH (Figure 2).



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