Genetic progression and the waiting time to cancer.

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 canc...

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Autores principales:	Niko Beerenwinkel, Tibor Antal, David Dingli, Arne Traulsen, Kenneth W Kinzler, Victor E Velculescu, Bert Vogelstein, Martin A Nowak
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2007
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/afe9188828234658a5998cdcda6705fc
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spelling	oai:doaj.org-article:afe9188828234658a5998cdcda6705fc2021-11-25T05:41:01ZGenetic progression and the waiting time to cancer.1553-734X1553-735810.1371/journal.pcbi.0030225https://doaj.org/article/afe9188828234658a5998cdcda6705fc2007-11-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.0030225https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Cancer 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.Niko BeerenwinkelTibor AntalDavid DingliArne TraulsenKenneth W KinzlerVictor E VelculescuBert VogelsteinMartin A NowakPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 3, Iss 11, p e225 (2007)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Niko Beerenwinkel Tibor Antal David Dingli Arne Traulsen Kenneth W Kinzler Victor E Velculescu Bert Vogelstein Martin A Nowak Genetic progression and the waiting time to cancer.
description	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.
format	article
author	Niko Beerenwinkel Tibor Antal David Dingli Arne Traulsen Kenneth W Kinzler Victor E Velculescu Bert Vogelstein Martin A Nowak
author_facet	Niko Beerenwinkel Tibor Antal David Dingli Arne Traulsen Kenneth W Kinzler Victor E Velculescu Bert Vogelstein Martin A Nowak
author_sort	Niko Beerenwinkel
title	Genetic progression and the waiting time to cancer.
title_short	Genetic progression and the waiting time to cancer.
title_full	Genetic progression and the waiting time to cancer.
title_fullStr	Genetic progression and the waiting time to cancer.
title_full_unstemmed	Genetic progression and the waiting time to cancer.
title_sort	genetic progression and the waiting time to cancer.
publisher	Public Library of Science (PLoS)
publishDate	2007
url	https://doaj.org/article/afe9188828234658a5998cdcda6705fc
work_keys_str_mv	AT nikobeerenwinkel geneticprogressionandthewaitingtimetocancer AT tiborantal geneticprogressionandthewaitingtimetocancer AT daviddingli geneticprogressionandthewaitingtimetocancer AT arnetraulsen geneticprogressionandthewaitingtimetocancer AT kennethwkinzler geneticprogressionandthewaitingtimetocancer AT victorevelculescu geneticprogressionandthewaitingtimetocancer AT bertvogelstein geneticprogressionandthewaitingtimetocancer AT martinanowak geneticprogressionandthewaitingtimetocancer
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Genetic progression and the waiting time to cancer.

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