Alterations in the chromosomal content of a cell compared to normal are known as polyploidy or aneuploidy. Polyploidy is a change that is a multiple of the haploid chromosome content while aneuploidy is a change in the chromosome content that is not a multiple of the haploid number. There are many cases demonstrating that polyploidy is reasonably well tolerated at the organismal level and that whole-genome duplications likely served to promote the evolution of species ( 1 ). However, this is not the case for aneuploidy where the gain or loss of individual chromosomes has been shown to cause lethality and the development of disease (1). Mitosis is a highly regulated process with various surveillance mechanisms in place to coordinate the correct segregation of genetic material between daughter cells. However, even in the presence of these checkpoints aneuploidy can occur, as chromosome missegregation is estimated to occur at a rate of once every 104–105 cell divisions in mammalian cells (2). Aneuploidy has long been known as a hallmark problem of tumor cells (3), and changes in chromosome number have been proposed as a mechanism by which tumor cells acquire additional copies of oncogenes or lose expression of tumor suppressor genes. thus driving the tumorigenic process. Interestingly, individuals with Down syndrome (DS) are at increased risk of developing leukemia, retinoblastoma, and germ cell tumors, but are less likely to develop other solid tumors (4, 5). As I develop my research team, I am trying to further define how the presence of an extra chromosome influences the fitness of mammalian cells and how these differences might provide insight into the role of aneuploidy in cancer… half of paper . .....ncer.References1. EM Torres, BR Williams, A. Amon, Genetics 179, 737 (June 2008).2. MJ Rosenstraus, L.A. Chasin, Genetics 90, 735 (December 1978).3. T. Boveri, Neu Folge 35, 67 (1902).4. H. Hasle, IH Clemmensen, M. Mikkelsen, Lancet 355, 165 (15 January 2000).5. D. Satge, AJ Sasco, B. Lacour, Int J Cancer 106, 297 (20 August 2003).6. BR Williams et al., Science 322, 703 (October 31, 2008).7. DJ Burgess et al., Proc Natl Acad Sci USA 105, 9053 (July 1, 2008).8. RJ DeBerardinis et al., Proc Natl Acad Sci USA 104, 19345 (4 December 2007).9. Z. Kovacevic, JD McGivan, Physiol Rev 63, 547 (April 1983).10. JK Hitzler, A. Zipursky, Nat Rev Cancer 5, 11 (January 2005).11. D. Bercovich et al., Lancet 372, 1484 (25 October 2008).12. L. Kearney et al., Blood 113, 646 (15 January 2009).13. A. Mensah et al., BMC Dev Biol 7, 131 (2007).