PMID- 16043196 OWN - NLM STAT- MEDLINE DCOM- 20051122 LR - 20191003 IS - 0025-5564 (Print) IS - 0025-5564 (Linking) VI - 197 IP - 1 DP - 2005 Sep TI - A comprehensive continuous-time model for the appearance of CGH signal due to chromosomal missegregations during mitosis. PG - 67-87 AB - Aneuploidy, the gain or loss of large regions of the genome, is a common feature in cancer cells. Irregularities in chromosomal copy number caused by missegregations of chromosomes during mitosis can be visualized by cytogenetic techniques including fluorescence in situ hybridization (FISH), spectral karyotyping (SKY) and comparative genomic hybridization (CGH). In the current work, we consider the propagation of irregular copy numbers throughout a cell population as the individual cells progress through ordinary mitotic cell cycles. We use an algebraic model to track the different copy numbers as states in a stochastic process, based on the model of chromosome instability of Gusev, Kagansky, and Dooley, and consider the average copy number of a particular chromosome within a cell population as a function of the cell division rate. We review a number of mathematical models for determining the length of the cell cycle, including the Smith-Martin transition probability model and the 'sloppy size' model of Wheals, Tyson and Diekmann. The program MITOSIM simulates the growth of a population of cells using the aforementioned models of the cell cycle. MITOSIM allows the cell population to grow, with occasional resampling, until the average copy number of a given chromosome in the population reaches a preset threshold signifying a positive copy number alteration in this region. MITOSIM calculates the relationship between the missegregation rate and the growth rate of the cell population. This allows the user to test hypotheses regarding the effect chromosomal aberrations have upon the cell cycle, cell growth rates, and time to population dominance. FAU - Desper, Richard AU - Desper R AD - Computational Biology Branch, National Center for Biotechnology Information, National Institutes of Health, Department of Health and Human Services, Building 38A, Room 6S608, 8600 Rockville Pike, Bethesda, MD, USA. FAU - Difilippantonio, Michael J AU - Difilippantonio MJ FAU - Ried, Thomas AU - Ried T FAU - Schaffer, Alejandro A AU - Schaffer AA LA - eng GR - Z99 CA999999/Intramural NIH HHS/United States PT - Comparative Study PT - Journal Article PL - United States TA - Math Biosci JT - Mathematical biosciences JID - 0103146 SB - IM MH - Aneuploidy MH - Chromosome Segregation/*genetics MH - Computer Simulation MH - Cytogenetics MH - Humans MH - Mathematics MH - Mitosis/*genetics MH - Models, Genetic MH - Models, Statistical MH - Neoplasms/genetics MH - Software PMC - PMC1356526 MID - NIHMS6178 EDAT- 2005/07/27 09:00 MHDA- 2005/12/13 09:00 PMCR- 2008/01/24 CRDT- 2005/07/27 09:00 PHST- 2004/08/10 00:00 [received] PHST- 2005/03/31 00:00 [revised] PHST- 2005/05/16 00:00 [accepted] PHST- 2005/07/27 09:00 [pubmed] PHST- 2005/12/13 09:00 [medline] PHST- 2005/07/27 09:00 [entrez] PHST- 2008/01/24 00:00 [pmc-release] AID - S0025-5564(05)00100-8 [pii] AID - 10.1016/j.mbs.2005.05.005 [doi] PST - ppublish SO - Math Biosci. 2005 Sep;197(1):67-87. doi: 10.1016/j.mbs.2005.05.005.