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 chromosome content that is not a multiple of the haploid number. There are many examples demonstrating that polyploidy is reasonably well tolerated at the organismal level, and 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 lead to death and disease development (1). Mitosis is a highly regulated process with various surveillance mechanisms in place to coordinate the appropriate 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 one in 104 to 105 cell divisions in mammalian cells (2). characteristic of cancer cells ( 3 ), and changes in chromosome number have been proposed as a mechanism by which cancer cells acquire additional copies of oncogenes or lose expression of tumor suppressor genes, thereby driving the tumorigenic process. Interestingly, people 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 grow my own research group, I seek to better 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. paper ......ncer.References1. EM Torres, BR Williams, A. Amon, Genetics 179, 737 (June 2008).2. MJ Rosenstraus, LA Chasin, Genetics 90, 735 (December 1978).3. T. Boveri, Neu Folge 35, 67 (1902).4. H. Hasle, IH Clemmensen, M. Mikkelsen, Lancet 355, 165 (January 15, 2000).5. D. Satge, AJ Sasco, B. Lacour, Int J Cancer 106, 297 (August 20, 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 (December 4, 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 (October 25, 2008).12. L. Kearney et al., Blood 113, 646 (January 15, 2009).13. A. Mensah et al., BMC Dev Biol 7, 131 (2007).