The role of chromosomal instability in tumor initiation

Martin A. Nowak, Natalia L. Komarova, Anirvan Sengupta, Prasad V. Jallepalli, Le Ming Shih, Bert Vogelstein, Christoph Lengauer

Research output: Contribution to journalArticlepeer-review

366 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)16226-16231
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number25
StatePublished - Dec 10 2002

ASJC Scopus subject areas

  • General


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