Nowak Martin A, Komarova Natalia L, Sengupta Anirvan, Jallepalli Prasad V, Shih Ie-Ming, Vogelstein Bert, Lengauer Christoph
Institute for Advanced Study, Princeton, NJ 08540, USA.
Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16226-31. doi: 10.1073/pnas.202617399. Epub 2002 Nov 21.
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.
染色体不稳定（CIN）是大多数人类癌症的一个决定性特征。CIN基因的突变增加了在细胞分裂过程中整条染色体或大部分染色体获得或丢失的可能性。CIN的结果是每个细胞中染色体数量的不平衡（非整倍体）以及杂合性丢失率的提高。癌症遗传学的一个主要问题是CIN或任何遗传不稳定性在多大程度上是一个早期事件，从而成为肿瘤进展的驱动力。在本文中，我们开发了一个数学框架来研究CIN对癌症体细胞进化的影响。具体来说，我们计算了CIN在肿瘤抑制基因失活之前启动结直肠癌发生过程的条件。
