The role of chromosomal instability in tumor initiation.
Chromosomal instability (CIN) is a defining characteristic of most human cancers. Mutation of CIN genes increases the probability that whole chromosomes or large fractions of chromosomes are gained or lost during cell division. The consequence of CIN is an imbalance in the number of chromosomes per cell (aneuploidy) and an enhanced rate of loss of heterozygosity. A major question of cancer genetics is to what extent CIN, or any genetic instability, is an early event and consequently a driving force for tumor progression. In this article, we develop a mathematical framework for studying the effect of CIN on the somatic evolution of cancer. Specifically, we calculate the conditions for CIN to initiate the process of colorectal tumorigenesis before the inactivation of tumor suppressor genes.
Nowak
Martin A
MA
Institute for Advanced Study, Princeton, NJ 08540, USA. nowak@ias.edu
Komarova
Natalia L
NL
Sengupta
Anirvan
A
Jallepalli
Prasad V
PV
Shih
Ie-Ming
IeM
Vogelstein
Bert
B
Lengauer
Christoph
C
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002869:Chromosome Aberrations; D019457:Chromosome Breakage; D002873:Chromosome Fragility / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics; D017491:Genes, APC; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D051379:Mice; D008957:Models, Genetic; D016296:Mutagenesis; D017354:Point Mutation; D012175:Retinoblastoma / Q000235:genetics; D013269:Stochastic Processes