Department of Biochemistry, University of Leicester University Road, Leicester, LEI 7RH, UK.
Am J Cancer Res. 2011;1(7):955-71. Epub 2011 Mar 29.
Most cancers progress with the accumulation of genetic mutations with time and this is frequently associated with the acquisition of genomic instability in the form of whole chromosome changes, chromosomal rearrangements, gene amplifications or smaller changes at the nucleotide level. Whole chromosome instability (W-CIN), characterised by aneuploidy, is a major form of genomic instability observed in human cancers and several lines of evidence now support the argument that W-CIN is a promoter of tumourigenesis rather than being a passenger event. The primary mechanism proposed for evolution of CIN is abnormalities in mitosis/cytokinesis. However, mutations in genes directly involved in controlling mitosis/cytokinesis are rare in human cancers and so the mechanisms underpinning the evolution of CIN in cancers are not currently clear. On the other hand, mutations in RAS or BRAF are frequently found in human cancers, many of which demonstrate CIN, suggesting a possible link between deregulated signaling through the RAS/RAF/MEK/ERK pathway and CIN. In this review, we focus on a potential relationship between deregulated RAS/RAF signaling and CIN, and discuss possible mechanisms connecting the two.
大多数癌症随着时间的推移会积累遗传突变，这通常与以全染色体改变、染色体重排、基因扩增或核苷酸水平较小变化的形式获得基因组不稳定性有关。全染色体不稳定性（W-CIN）以非整倍体为特征，是人类癌症中观察到的主要基因组不稳定性形式，现在有几条证据支持这样的观点，即 W-CIN 是肿瘤发生的促进因素，而不是乘客事件。CIN 进化的主要机制是有丝分裂/胞质分裂异常。然而，直接参与控制有丝分裂/胞质分裂的基因中的突变在人类癌症中很少见，因此癌症中 CIN 进化的机制目前尚不清楚。另一方面，RAS 或 BRAF 中的突变在人类癌症中经常发现，其中许多癌症表现出 CIN，这表明 RAS/RAF/MEK/ERK 通路中信号的失调与 CIN 之间可能存在联系。在这篇综述中，我们重点关注失调的 RAS/RAF 信号与 CIN 之间的潜在关系，并讨论连接两者的可能机制。
