Exploring the relationship between neutral and selective mutations in cancer

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The transformation of normal cells into cancerous cells is an evolutionary process. Populations of precancerous cells reproduce, mutate, and compete for resources. Some of these mutations eventually lead to cancer. We calculate the probability of developing cancer under a set of simplifying assumptions and then elaborate these calculations, culminating in a simple simulation of the cell dynamics. The agent-based model allows us to examine the interactions of mutations critical for the development of cancer that are either evolutionarily neutral or selective. We can also examine the interaction of these mutations with a "mutator phenotype" derived from mutations that raise the mutation rate for the entire cell. The simulations suggest that there must be at least two selectively neutral mutations necessary for the development of cancer and that preventive treatments will be most effective when they increase this number. The model also suggests that selective mutations facilitate the development of cancer, so that the more selective mutations necessary for the development of cancer, the greater the chance of developing it.

Original languageEnglish (US)
Pages (from-to)325-345
Number of pages21
JournalArtificial Life
Volume6
Issue number4
StatePublished - 2000
Externally publishedYes

Fingerprint

Cancer
Mutation
Cells
Neoplasms
Cell
Mutation Rate
Necessary
Relationships
Agent-based Model
Interaction
Phenotype
Simulation
Entire
Calculate
Resources
Population

Keywords

  • Agent-based model
  • Cancer
  • Evolution
  • Mutator phenotype
  • Progression

ASJC Scopus subject areas

  • Artificial Intelligence
  • Computational Theory and Mathematics
  • Control and Systems Engineering
  • Theoretical Computer Science

Cite this

Exploring the relationship between neutral and selective mutations in cancer. / Maley, Carlo; Forrest, Stephanie.

In: Artificial Life, Vol. 6, No. 4, 2000, p. 325-345.

Research output: Contribution to journalArticle

@article{5c51bb41ab6b44afa276dd0390026f2b,
title = "Exploring the relationship between neutral and selective mutations in cancer",
abstract = "The transformation of normal cells into cancerous cells is an evolutionary process. Populations of precancerous cells reproduce, mutate, and compete for resources. Some of these mutations eventually lead to cancer. We calculate the probability of developing cancer under a set of simplifying assumptions and then elaborate these calculations, culminating in a simple simulation of the cell dynamics. The agent-based model allows us to examine the interactions of mutations critical for the development of cancer that are either evolutionarily neutral or selective. We can also examine the interaction of these mutations with a {"}mutator phenotype{"} derived from mutations that raise the mutation rate for the entire cell. The simulations suggest that there must be at least two selectively neutral mutations necessary for the development of cancer and that preventive treatments will be most effective when they increase this number. The model also suggests that selective mutations facilitate the development of cancer, so that the more selective mutations necessary for the development of cancer, the greater the chance of developing it.",
keywords = "Agent-based model, Cancer, Evolution, Mutator phenotype, Progression",
author = "Carlo Maley and Stephanie Forrest",
year = "2000",
language = "English (US)",
volume = "6",
pages = "325--345",
journal = "Artificial Life",
issn = "1064-5462",
publisher = "MIT Press Journals",
number = "4",

}

TY - JOUR

T1 - Exploring the relationship between neutral and selective mutations in cancer

AU - Maley, Carlo

AU - Forrest, Stephanie

PY - 2000

Y1 - 2000

N2 - The transformation of normal cells into cancerous cells is an evolutionary process. Populations of precancerous cells reproduce, mutate, and compete for resources. Some of these mutations eventually lead to cancer. We calculate the probability of developing cancer under a set of simplifying assumptions and then elaborate these calculations, culminating in a simple simulation of the cell dynamics. The agent-based model allows us to examine the interactions of mutations critical for the development of cancer that are either evolutionarily neutral or selective. We can also examine the interaction of these mutations with a "mutator phenotype" derived from mutations that raise the mutation rate for the entire cell. The simulations suggest that there must be at least two selectively neutral mutations necessary for the development of cancer and that preventive treatments will be most effective when they increase this number. The model also suggests that selective mutations facilitate the development of cancer, so that the more selective mutations necessary for the development of cancer, the greater the chance of developing it.

AB - The transformation of normal cells into cancerous cells is an evolutionary process. Populations of precancerous cells reproduce, mutate, and compete for resources. Some of these mutations eventually lead to cancer. We calculate the probability of developing cancer under a set of simplifying assumptions and then elaborate these calculations, culminating in a simple simulation of the cell dynamics. The agent-based model allows us to examine the interactions of mutations critical for the development of cancer that are either evolutionarily neutral or selective. We can also examine the interaction of these mutations with a "mutator phenotype" derived from mutations that raise the mutation rate for the entire cell. The simulations suggest that there must be at least two selectively neutral mutations necessary for the development of cancer and that preventive treatments will be most effective when they increase this number. The model also suggests that selective mutations facilitate the development of cancer, so that the more selective mutations necessary for the development of cancer, the greater the chance of developing it.

KW - Agent-based model

KW - Cancer

KW - Evolution

KW - Mutator phenotype

KW - Progression

UR - http://www.scopus.com/inward/record.url?scp=0034278890&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034278890&partnerID=8YFLogxK

M3 - Article

VL - 6

SP - 325

EP - 345

JO - Artificial Life

JF - Artificial Life

SN - 1064-5462

IS - 4

ER -