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Genomic instability

What came first?

Nature Reviews Cancer volume 3, page 9 (2003)Cite this article

They started by considering the six states, with respect to APC inactivation and CIN, that any cell in the colonic crypt could be in. Cells could have none, one or two functional APC alleles, in the presence or absence of CIN. They then determined how, and with what rate, a cell could progress from one state to the next by considering parameters such as mutation rate, loss of heterozygosity rate in normal and CIN cells, reproductive rate of APC−/− and CIN cells, and the number of dominant CIN genes.

They calculated the probability that the system reaches the state X2 (APC inactivation occurs in the absence of CIN) or Y2 (APC inactivation occurs in the presence of CIN) first, and therefore whether CIN could cause inactivation of the second APC allele. For the second scenario to occur, the number of CIN genes must exceed a certain threshold value. This number depends on several factors, including the selective cost of CIN and the effective number of stem cells per crypt. For a wide range of realistic parameter values, the crucial number of CIN genes is as low as 1–10.

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References

ORIGINAL RESEARCH PAPER

  1. Nowak, M. A. et al. The role of chromosomal instability in tumor initiation. Proc. Natl Acad. Sci. USA 21 Nov 2002 [epub ahead of print].

FURTHER READING

  1. Fodde, R. et al. APC, signal transduction and genetic instability in colorectal cancer. Nature Rev. Cancer 1, 55–67 (2001)

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Authors
  1. Emma Greenwood
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Greenwood, E. What came first?. Nat Rev Cancer 3, 9 (2003). https://doi.org/10.1038/nrc979

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  • DOI: https://doi.org/10.1038/nrc979

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