Loeb L A, Christians F C
Department of Pathology, Joseph Gottstein Memorial Cancer Research Laboratory, University of Washington, Seattle 98195, USA.
Mutat Res. 1996 Feb 19;350(1):279-86. doi: 10.1016/0027-5107(95)00117-4.
Increasing evidence indicates that most human cancers contain multiple mutations. The exact number of mutations, their origin, and types remain to be determined. An over-riding question is whether the multiple mutations that accumulate in cancers is rate-limiting for the carcinogenic process. In this review we consider the argument that the large numbers of mutations routinely reported in human cancers cannot be accounted for by the rate of spontaneous mutation observed in normal human cells. We will analyze different mechanisms that might account for the accumulation of mutations in cancer cells. We conclude that cancer cells are genetically unstable; i.e., they exhibit a mutator phenotype. The recent reports of microsatellite instability in a variety of human cancers have provided the first strong evidence for the presence of a mutator phenotype in human cancers. However, we still lack information about the relationship between microsatellite instability and mutations that allow cancer cells to proliferate, invade, and metastasize.
越来越多的证据表明，大多数人类癌症都包含多种突变。突变的确切数量、起源和类型仍有待确定。一个首要问题是，癌症中积累的多种突变是否是致癌过程的限速因素。在这篇综述中，我们探讨这样一种观点：人类癌症中常规报道的大量突变无法用正常人类细胞中观察到的自发突变率来解释。我们将分析可能导致癌细胞中突变积累的不同机制。我们得出结论，癌细胞在基因上是不稳定的；也就是说，它们表现出突变体表型。最近关于多种人类癌症中微卫星不稳定性的报道，为人类癌症中存在突变体表型提供了首个有力证据。然而，我们仍然缺乏关于微卫星不稳定性与使癌细胞增殖、侵袭和转移的突变之间关系的信息。
