Genetic Progression and the Waiting Time to Cancer
By Niko Beerenwinkel, T. Antal, D. Dingli, Arne Traulsen, Kenneth W. Kinzler, Victor E. Velculescu, Bert Vogelstein, Martin A. Nowak. PLoS Comput. Biol., 2007
421 citations recorded by the source corpus.
Cancer results from genetic alterations that disturb the normal cooperative behavior of cells. Recent high-throughput genomic studies of cancer cells have shown that the mutational landscape of cancer is complex and that individual cancers may evolve through mutations in as many as 20 different cancer-associated genes. We use data published by Sjöblom et al. (2006) to develop a new mathematical model for the somatic evolution of colorectal cancers. We employ the Wright-Fisher process for exploring the basic parameters of this evolutionary process and derive an analytical approximation for the expected waiting time to the cancer phenotype. Our results highlight the relative importance of selection over both the size of the cell population at risk and the mutation rate. The model predicts that the observed genetic diversity of cancer genomes can arise under a normal mutation rate if the average selective advantage per mutation is on the order of 1%. Increased mutation rates due to genetic instability would allow even smaller selective advantages during tumorigenesis. The complexity of cancer progression can be understood as the result of multiple sequential mutations, each of which has a relatively small but positive effect on net cell growth.
Subfields: Cancer Research, Genetics, Modeling and Simulation
View Paper: https://www.semanticscholar.org/paper/7db548d9db74f64ccecb028e3f2fa3bd386bf1cf
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Cancer Research
- Bert Vogelstein
- Kenneth W. Kinzler
- Niko Beerenwinkel
- Moritz Gerstung
- Hannah Carter
- A. Bardelli
- L. Diaz
In Genetics
- Martin A. Nowak
- Niko Beerenwinkel
- Moritz Gerstung
- Florian Markowetz
- Roland F. Schwarz
- Su-Chan Park
- Jason Schweinsberg
- Bert Vogelstein
Citations in the corpus
- A spatial model predicts that dispersal and cell turnover limit intratumour heterogeneity (2015, background): “Most attempts at explaining the genetic make-up of tumors assume well-mixed populations of cells and do not incorporate spatial constraints [6,7,8,9,10,11].”
- Cancer Evolution: Mathematical Models and Computational Inference (2014, methodology): “…et al. 2005a) Mixture of HOTs forest discrete monotone yes ML via SEM hotmixe (Tofigh et al. 2011) CBN DAG discrete monotone yes ML cbnf (Beerenwinkel et al. 2007b) CT-CBN DAG waiting time monotone no ML via EM ct-cbng (Beerenwinkel and Sullivant 2009) Hidden CBN DAG waiting time…”
- The Speed of Evolution in Large Asexual Populations (2009, methodology): “In this section we follow the particul arly simple and transparent derivation presented in [2].”
- CLONAL EVOLUTION IN CANCER (2012, background): “The traditional model of clonal evolution suggests that a series of clonal expansions grows to dominate the neoplasm ('selective sweeps'”
- Accumulation of driver and passenger mutations during tumor progression (2009, methodology): “(22) previously modeled tumor evolution using a Wright–Fisher process.”
- Rigorous results for a population model with selection II: genealogy of the population (2014, result): “This is again quite different from the results for the model studied in this paper, where the distribution of fitnesses of individuals in the population has Gaussian-like tails; see, for example, [2, 11, 26, 28, 29].”