Cancer as an evolutionary and ecological process

Merlo, Lauren M.F.; Pepper, John W.; Reid, Brian J.; Maley, Carlo C.

doi:10.1038/nrc2013

Cited by 1,543 publications

(1,334 citation statements)

References 154 publications

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“…Why such heterogeneity exists remains unclear [Merlo et al 2006, Almendro et al 2013, because clones that have a proliferative advantage within the tumour are expected to drive other subclones to extinction. In the light of evolutionary game theory, however, stable intra-tumor heterogeneity is easily explained as a stable polymorphic equilibrium resulting from the non-linear benefit of growth factors [Archetti et al 2015].…”

Section: Implications For Cancer Researchmentioning

confidence: 99%

“…While it is now understood that cancer is a process of clonal selection [Cairns 1975, Nowell 1976, Crespi & Summers 2005, Merlo et al 2006, Greaves & Maley 2012, and game theory has often been mentioned as a relevant for cancer research [Gatenby & Maini 2003, Merlo et al 2006, Axelrod et al 2006, Lambert et al 2011, the study of growth factors in the framework of evolutionary game theory is still limited. Tomlinson [1997] and Tomlinson & Bodmer [1997] used the hawk-dove game, to explain why game theory can be used to understand conflict and cooperation between cancer cells; subsequent papers [Bach et al 2001, Dingli et al 2009, Basanta et al 2008a,b, 2011, 2012, Gerstung et al 2011 have extended that model to up to 4 strategies.…”

Section: Further Developments Of the Modelmentioning

confidence: 99%

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Cooperation among cancer cells as public goods games on Voronoi networks

Archetti

2016

Journal of Theoretical Biology

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Cancer cells produce growth factors that diffuse and sustain tumor proliferation, a form of cooperation among cancer cells that can be studied using mathematical models of public goods in the framework of evolutionary game theory. Cell populations, however, form heterogeneous networks that cannot be described by regular lattices or scale-free networks, the types of graphs generally used in the study of cooperation. To describe the dynamics of growth factor production in populations of cancer cells, I study public goods games on Voronoi networks, using a range of non-linear benefits that account for the known properties of growth factors, and different types of diffusion gradients. The results are surprisingly similar to those obtained on regular graphs and different from results on scale-free networks, revealing that network heterogeneity per se does not promote cooperation when public goods diffuse beyond one-step neighbours. The exact shape of the diffusion gradient is not crucial, however, whereas the type of non-linear benefit is an essential determinant of the dynamics. Public goods games on Voronoi networks can shed light on intra-tumor heterogeneity, the evolution of resistance to therapies that target growth factors, and new types of cell therapy.

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Section: Implications For Cancer Researchmentioning

confidence: 99%

Section: Further Developments Of the Modelmentioning

confidence: 99%

Cooperation among cancer cells as public goods games on Voronoi networks

Archetti

2016

Journal of Theoretical Biology

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“…C ancer is a somatic evolutionary process in which mutations render cells non-cooperative and overly proliferative [1][2][3] . Selectively advantageous driver mutations accumulate in multiple rounds of clonal expansions together with hitch-hiking, selectively neutral passenger mutations 1,4 .…”

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confidence: 99%

Reliable detection of subclonal single-nucleotide variants in tumour cell populations

et al. 2012

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According to the clonal evolution model, tumour growth is driven by competing subclones in somatically evolving cancer cell populations, which gives rise to genetically heterogeneous tumours. Here we present a comparative targeted deep-sequencing approach combined with a customised statistical algorithm, called deepsnV, for detecting and quantifying subclonal single-nucleotide variants in mixed populations. We show in a rigorous experimental assessment that our approach is capable of detecting variants with frequencies as low as 1/10,000 alleles. In selected genomic loci of the TP53 and VHL genes isolated from matched tumour and normal samples of four renal cell carcinoma patients, we detect 24 variants at allele frequencies ranging from 0.0002 to 0.34. moreover, we demonstrate how the allele frequencies of known single-nucleotide polymorphisms can be exploited to detect loss of heterozygosity. our findings demonstrate that genomic diversity is common in renal cell carcinomas and provide quantitative evidence for the clonal evolution model.

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“…The evolutionary framework has improved our understanding of the genetic basis of cancer [13][14][15] . Although the somatic evolution of cancer cells is reminiscent of the evolution of organisms, the two differ in many ways, such as timescale, effective population size, mutation rate, and outcome of the evolution 15,16 . Understanding differences between the two can improve our understanding of the genetic basis of cancer.…”

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confidence: 99%

DNA replication timing and selection shape the landscape of nucleotide variation in cancer genomes

2012

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Cancer cells evolve from normal cells by somatic mutations and natural selection. Comparing the evolution of cancer cells and that of organisms can elucidate the genetic basis of cancer. Here we analyse somatic mutations in > 400 cancer genomes. We find that the frequency of somatic single-nucleotide variations increases with replication time during the s phase much more drastically than germ-line single-nucleotide variations and somatic large-scale structural alterations, including amplifications and deletions. The ratio of nonsynonymous to synonymous single-nucleotide variations is higher for cancer cells than for germ-line cells, suggesting weaker purifying selection against somatic mutations. Among genes with recurrent mutations only cancer driver genes show evidence of strong positive selection, and late-replicating regions are depleted of cancer driver genes, although enriched for recurrently mutated genes. These observations show that replication timing has a prominent role in shaping the single-nucleotide variation landscape of cancer cells.

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Cancer as an evolutionary and ecological process

Cited by 1,543 publications

References 154 publications

Cooperation among cancer cells as public goods games on Voronoi networks

Cooperation among cancer cells as public goods games on Voronoi networks

Reliable detection of subclonal single-nucleotide variants in tumour cell populations

DNA replication timing and selection shape the landscape of nucleotide variation in cancer genomes

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