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The study of the genomic imbalances in a variety of different diseases, including cancer, is a major step towards the understanding of disease development. In cancer cells, for example, DNA copy number increases have been shown to be one of the mechanisms by which oncogenes and drug resistance genes can be activated, whereas loss of DNA material may cause inactivation of tumor suppressor genes. Knowledge of copy-number aberrations can have also immediate clinical use in diagnosis and in some cases can provide useful prognostic information.
One of the main research topics in our laboratory is based on the analysis of the genomic imbalances in solid tumors. Our aim is to identify the correlation between the gene dosage and the levels of transcript message. To address this question we use high density oligonucleotide-based CGH microarrays together with gene expression microarrays.
Colorectal cancer holds specific aneuploidies that might represent obligate events for its tumorigenesis. So far, specific genes have been identified as target genes that selectively lead to the gain or loss of chromosomes. Nevertheless, some trisomies are not yet associated to any specific cancer genes. By studying the genomic and transcriptional profiling of primary colon and rectum cancers we inferred signatures of genes that might lead to the specific genomic profiling of colorectal cancers.
Structural submicroscopic rearrangements, subtle genome alterations and the transcriptional output linked to the genes that are affected also represent a major focus of interest. Combination of SKY, FISH and microarray methodologies applied to a set of cell lines will allow us to identify novel, hitherto undetected chromosomal alterations, and will let us know a yet underestimated mechanism for the generation of allelic imbalances.