Multiple mutations in human cancers
Multiple mutations in human cancers
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DOI：
10.1016/0027-5107(95)00117-4
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发表时间：
1996-02-19
影响因子：
2.3
通讯作者：
Christians, FC
中科院分区：
文献类型：
--
作者：
Loeb, LA;Christians, FC
越来越多的证据表明，大多数人类癌症都含有多种突变。突变的确切数量、起源和类型仍有待确定。一个最重要的问题是，癌症中积累的多种突变是否会限制致癌过程的速率。在这篇综述中，我们考虑了这样的论点：人类癌症中常规报道的大量突变不能用正常人类细胞中观察到的自发突变率来解释。我们将分析可能解释癌细胞突变积累的不同机制。我们得出的结论是，癌细胞的基因不稳定；即，它们表现出突变表型。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表型提供了第一个强有力的证据。然而，我们仍然缺乏关于微卫星不稳定性与癌细胞增殖、侵袭和转移的突变之间关系的信息。
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.