Document Detail


Gene expression profiling and gene copy-number changes in malignant mesothelioma cell lines.
MedLine Citation:
PMID:  17620293     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Malignant mesothelioma (MM) is an asbestos-induced tumor that acquires aneuploid DNA content during the tumorigenic process. We used instable MM cell lines as an in vitro model to study the impact of DNA copy-number changes on gene expression profiling, in the course of their chromosomal redistribution process. Two MM cell lines, PMR-MM2 (early passages of in vitro culture) and PMR-MM7 (both early and late passages of in vitro culture), were cytogenetically characterized. Genomic gains and losses were precisely defined using microarray-based comparative genomic hybridization (array-CGH), and minimal overlapping analysis led to the identification of the common unbalanced genomic regions. Using the U133Plus 2.0 Affymetrix gene chip array, we analyzed PMR-MM7 early and late passages for genome-wide gene expression, and correlated the differentially expressed genes with copy-number changes. The presence of a high number of genetic imbalances occurring from early to late culture steps reflected the tendency of MM cells toward genomic instability. The selection of specific chromosomal abnormalities observed during subsequent cultures demonstrated the spontaneous evolution of the cancer cells in an in vitro environment. MM cell lines were characterized by copy-number changes associated with the TP53 apoptotic pathway already present at the first steps of in vitro culture. Prolonged culture led to acquisition of additional chromosomal copy-number changes associated with dysregulation of genes involved in cell adhesion, regulation of mitotic cell cycle, signal transduction, carbohydrate metabolism, motor activity, glycosaminoglycan biosynthesis, protein binding activity, lipid transport, ATP synthesis, and methyltransferase activity.
Authors:
Claudia Zanazzi; Remko Hersmus; Imke M Veltman; Ad J M Gillis; Ellen van Drunen; H Berna Beverloo; Joost P J J Hegmans; Marielle Verweij; Bart N Lambrecht; J Wolter Oosterhuis; Leendert H J Looijenga
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Genes, chromosomes & cancer     Volume:  46     ISSN:  1045-2257     ISO Abbreviation:  Genes Chromosomes Cancer     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-08-07     Completed Date:  2007-10-25     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9007329     Medline TA:  Genes Chromosomes Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  895-908     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2007 Wiley-Liss, Inc.
Affiliation:
Department of Pathology, Erasmus Medical Center, Daniel den Hoed Cancer Center, Josephine Nefkens Institute, Rotterdam, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Blotting, Western
Chromosome Aberrations*
Chromosome Mapping
Chromosomes, Human / genetics*
Gene Dosage / genetics*
Gene Expression Profiling / methods*
Genome, Human / genetics
Humans
In Situ Hybridization, Fluorescence
Mesothelioma / genetics*,  metabolism
Nucleic Acid Hybridization
Oligonucleotide Array Sequence Analysis / methods*
Spectral Karyotyping
Tumor Markers, Biological / genetics,  metabolism
Tumor Suppressor Protein p53 / genetics,  metabolism
Chemical
Reg. No./Substance:
0/Tumor Markers, Biological; 0/Tumor Suppressor Protein p53

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