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Crick Lecture 2012: Consequences of Aneuploidy

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Aneuploidy is defined as a chromosome number that is not a multiple of the haploid complement. Almost a century ago, Theodor Boveri suggested a possible link between aneuploidy and cancer, a disease associated with high proliferative ability. On the other hand, aneuploidy at the organismal level is associated with severe developmental abnormalities and death in all species analyzed to date. These results raise an interesting conundrum. How is it possible that the presence of a single additional chromosome is associated with developmental defects characterized by growth restriction, yet in the context of cancer severe karyotypic abnormalities exist in cells with high proliferative abilities? To shed light on the relationship between aneuploidy and cancer we determined how aneuploidy affects the physiology and differentiation of normal cells. We generated 20 strains of budding yeast and 4 primary mouse cell lines bearing an extra copy of one or more of chromosomes. The analysis of these cell lines revealed chromosome specific phenotypes and traits shared by most aneuploid cell lines and strains. The importance of these characteristics in tumor evolution and development of new treatment strategies will be presented.

This talk is part of the MRC LMB Seminar Series series.

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