Department of Biomedical Engineering, Center for Complex Biological Systems, University of California Irvine, Irvine, California, United States of America.
PLoS One. 2011;6(10):e25978. doi: 10.1371/journal.pone.0025978. Epub 2011 Oct 6.
Normal human cells require a series of genetic alterations to undergo malignant transformation. Direct sequencing of human tumors has identified hundreds of mutations in tumors, but many of these are thought to be unnecessary and a result of, rather than a cause of, the tumor. The exact number of mutations to transform a normal human cell into a tumor cell is unknown. Here I show that male gonadal germ cell tumors, the most common form of testicular cancers, occur after four mutations. I infer this by constructing a mathematical model based upon the multi-hit hypothesis and comparing it to the age-specific incidence data. This result is consistent with the multi-hit hypothesis, and implies that these cancers are genetically or epigenetically predetermined at birth or an early age.
正常人类细胞需要经历一系列遗传改变才能发生恶性转化。对人类肿瘤的直接测序已经鉴定出肿瘤中有数百种突变，但许多突变被认为是不必要的，是肿瘤的结果而不是原因。将正常人类细胞转化为肿瘤细胞所需的突变数量尚不清楚。在这里，我表明最常见的睾丸癌——生殖细胞肿瘤，是在发生四次突变后发生的。我通过构建一个基于多击假说的数学模型，并将其与特定年龄的发病率数据进行比较，推断出这一点。这一结果与多击假说一致，意味着这些癌症在出生或早年就已经在遗传或表观遗传上被预先确定了。
