Host genetics and tumour metastasis.
Host genetics and tumour metastasis.
复制标题
宿主遗传学和肿瘤转移。
DOI：
10.1038/sj.bjc.6601590
复制
发表时间：
2004-02-23
影响因子：
8.8
通讯作者：
Hunter, K W
中科院分区：
文献类型：
--
作者：
Hunter, K W
转移，即肿瘤在继发部位的扩散和生长，是一种极其重要的临床事件，因为大多数癌症死亡率与转移性肿瘤有关，而不是与原发性肿瘤有关。尽管转移在临床环境中很重要，但实际过程效率极低。每天有数百万的肿瘤细胞进入血管系统;然而，很少有继发性肿瘤形成。解释这种低效率的经典假设是肿瘤中发生的一系列继发性事件，导致一小群细胞能够完成成功定植远端部位所需的所有步骤。然而，最近的发现表明，从大块肿瘤组织中的基因表达谱预测转移倾向的能力与原发性肿瘤中仅一小部分细胞亚群获得转移能力不一致，这表明转移能力可能是通过起始致癌突变在肿瘤中预先编程的。支持这两种看似不相容的理论的数据都存在。因此，为了协调观察到的结果，需要将额外的变量添加到转移性无效模型中。一个可能解释这种差异的变量是遗传背景效应。研究表明，肿瘤产生的遗传背景可能对肿瘤转移的能力和基因表达谱产生重大影响。因此，观察结果可以通过结合这些理论来调和，遗传背景影响转移效率和预测基因表达谱，随后发生促进转移的突变和表观遗传事件。如果遗传背景是转移效率的重要决定因素，那么它将对转移性疾病的临床预测和治疗以及潜在预防策略的设计具有重要意义。
Metastasis, the spread and growth of tumours at secondary sites, is an extremely important clinical event, since a majority of cancer mortality is associated with the metastatic tumours, rather than the primary tumour. In spite of the importance of metastasis in the clinical setting, the actual process is extremely inefficient. Millions of tumour cells can be shed into the vasculature daily; yet, few secondary tumours are formed. The classical hypothesis explaining the inefficiency was a series of secondary events occurring in the tumour, resulting in a small subpopulation of cells capable of completing all of the steps required to successfully colonise a distant site. However, recent discoveries demonstrating the ability to predict metastatic propensity from gene expression profiles in bulk tumour tissue are not consistent with only a small subpopulation of cells in the primary tumour acquiring metastatic ability, suggesting that metastatic ability might be pre-programmed in tumours by the initiating oncogenic mutations. Data supporting both of these seemingly incompatible theories exist. Therefore, to reconcile the observed results, additional variables need to be added to the model of metastatic inefficiency. One possible variable that might explain the discrepancies is genetic background effects. Studies have demonstrated that the genetic background on which a tumour arises on can have significant affects on the ability of the tumour to metastasise and on gene expression profiles. Thus, the observations could be reconciled by combining the theories, with genetic background influencing both metastatic efficiency and predictive gene expression profiles, upon which, subsequently, metastasis-promoting mutational and epigenetic events occur. If the genetic background is an important determinant of metastatic efficiency, it would have significant implications for the clinical prediction and treatment of metastatic disease, as well as for the design of potential prevention strategies.