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2006 Abstracts: Identification of chromosomal domains of differential gene expression in colorectal cancer by comparative chromosomal gene expression analysis (CCGEA)
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Identification of chromosomal domains of differential gene expression in colorectal cancer by comparative chromosomal gene expression analysis (CCGEA)
Joern Groene1, Stefan Roepke2, Maya Heinze1, Heinz J Buhr1, Eike Staub2; 1Department of Surgery, Charite Universitaetsmedizin Berlin, Berlin, Germany; 2Max Planck Institute for Molecular Genetics, Berlin, Germany

Cancer development is accompanied by genetic phenomena that influence gene expression in large chromosomal regions like deletion and amplification of chromosome parts or alterations of chromatin structure. However, little is known about effects of such regional phenomena on mRNA expression levels of genes. In this study we present a visualisation method for gene expression imbalanced chromosomal regions at much higher resolution than conventional technologies, called CCGEA (comparative chromosomal gene expression analysis). We investigated genome-wide gene expression in a panel of 50 microdissected samples of paired colorectal carcinoma (CRC) and normal epithelial tissue from 25 patients using large scale oligonucleotide arrays (~33.000 genes). CCGEA allowed the identification of several chromosomal domains with differential expression patterns at high resolution. We observed that regions that are frequently deleted in colon cancer tend to show reduced expression. Regions that are known to be amplified in colorectal tumors tend to show predominantly an increase, but occasionally a decrease of mRNA levels. The majority of chromosomal regions that are linked to hereditary colorectal cancer in the literature show deregulated expression. Many known genes implicated in other tumors localize to chromosomal domains of deregulated expression in CRC. We conclude that DNA copy number are likely to influence mRNA expression levels in CRC, although especially for amplifications the direction of influence is yet unpredictable. The knowledge of such integration of mRNA expression profiles along the chromosomes may provide alternative markers for cancer detection, prognosis and/or strategic therapeutic applications.


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