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Abstract: This project aims at elucidating factors involved in CIN and age-dependent aneuploidy. We want to address the hypothesis whether CIN or aneuploidy is caused by specific genetic alterations in a single gene or whether it is the consequence of mutations in several or a large number of genes. The project consists of three different steps: In a first, mainly descriptive step, we will employ latest 3D-multicolor FISH imaging techniques directly on tissue sections or on single cell suspensions to identify CIN/aneuploid regions in real biological material. In a second step, we will apply to these CIN/aneuploid regions our unbiased whole genome amplification strategies for subsequent array-CGH. This strategy will yield a high-resolution analysis of the genome of the respective areas or of individual cells. Regions within the tumor genome, which are commonly gained or lost will pinpoint locations of genes, which may be involved in the occurrence of CIN and aneuploidy. Candidate genes identified by this approach will be sequenced. The third, functional step, involves RNAi for gene knockdown of selected genes to verify that their reduced function has indeed an impact on chromosomal stability. Thus, this project combines both descriptive in vivo and functional in vitro technologies to derive significant biological conclusions.

Funded by: FWF, Fonds zur Förderung der Wissenschaftlichen Forschung, Wien, Austria