Genetic instability is not a requirement for tumor development.
Genetic instability is not a requirement for tumor development.
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DOI：
10.1158/0008-5472.can-07-6544
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发表时间：
2008-05-15
期刊：
影响因子：
11.2
通讯作者：
Beckman RA
中科院分区：
文献类型：
--
作者：
Bodmer W;Bielas JH;Beckman RA
这种观点起源于20世纪早期，即每一种癌症都是一个独立的体细胞进化过程，这种观点已被现代分子方法充分证实（1-3）。增加肿瘤生长机会的遗传和表观遗传变化依次被选择。然而，人们经常认为，正常的突变率不足以解释产生癌症所需的步骤数量。这导致了一种假设，即散发性癌症的体细胞进化需要基因组的不稳定性。这种不稳定性被认为是由于基因突变率的增加或染色体异常产生率的增加（4-6）。在某些类型的散发性癌症中，由于参与DNA修复的基因突变的存在，突变率增加，而且事实上，很大比例的癌症，特别是常见的癌症，具有严重紊乱的核型，这显然支持了这一假设。然而，基因组不稳定的论点似乎忽视了自然选择的力量，而自然选择对达尔文进化论的任何过程都是如此重要。
The idea, originating in the early years of the 20th century, that each cancer is an independent somatic evolutionary process has been abundantly confirmed by modern molecular approaches (1–3). Genetic and epigenetic changes that increase the chance of outgrowth of the developing tumor are successively selected for. It has, however, often been argued that normal mutation rates are not sufficient to explain the number of steps that seem to be needed for giving rise to a cancer. This has led to the hypothesis that there is a requirement for genomic instability in the somatic evolution of sporadic cancers. The instability is assumed to be due to an increase in gene mutation rates or to an increase in the rate of production of chromosomal abnormalities (4–6). In apparent support of this hypothesis is the observation of increased mutation rates in certain types of sporadic cancers due to the presence of mutations in genes involved in DNA repair, and the fact that a high proportion of cancers, especially the common carcinomas, have grossly deranged karyotypes. The argument for genomic instability, however, seems to ignore the power of natural selection, which is so fundamental to any process of Darwinian evolution.