Distribution of numerical aberrations in human cancers predicted by the presence/absence of chromosomal instability and aneuploidy-dependent selection.

<p>The expected distributions according to different conditions of chromosomal mis-segregation and selection were predicted by simulations as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070445#pone-0070445-g006" target="_blank">Figure 6</a>. In each graph, the reported data for Wilms tumour (WT, black circles) and colorectal cancer (CRC, red circles) are included for comparison. (A) The expected distribution (open blue circles) of numerical changes in a setting with chromosomal instability (CIN) in the absence of aneuploidy-dependent negative selection (<i>s</i>) is binomial-like with a high modal number of aberrations per tumour. All data points from 10 independent simulations were included. (B) A setting with CIN present but with <i>s</i> values similar to normal fibroblasts, results in a distribution with far fewer aneusomies than reported in WT and CRC. The same conditions, but with absence of CIN (C and D) result in similar distributions as when CIN is included, but with fewer abnormalities. (E) Attenuated aneusomy-dependent negative selection (<i>s</i> set as a span corresponding to the magnitude found in cancer cell lines) and with CIN present predicts a distribution of numerical changes highly similar to reported data. (F) In contrast, attenuated negative selection combined with absence of CIN results in distribution skewed towards fewer numerical aberrations than observed in WT and CRC.