Den Otter W, Koten J W
Department of Functional Morphology, Utrecht University, The Netherlands.
Anticancer Res. 1999 Nov-Dec;19(6A):4845-52.
Human life can be described as the clonal development of a fertilized egg. During cell proliferation in this clone among others cancer-specific mutations arise. Supposing that about 10(16) cells are produced in a lifetime; that the mutation frequency is about 10(-6) per gene per cell generation; that cells can go through about 60 cell divisions; and that cancer arises about once in a lifetime, carcinogenesis is likely to depend on 4 cancer-specific mutations. The advantage of a 4-mutation model over a multimutational model is that it implies far more predictions that can be tested. The 4-mutation model accurately predicts the age/incidence relation of tumors and the prevalence of cancer in the various organs. It further explains the increased tumor incidence in persons with an inherited cancer gene; and the well-known histological stages of carcinogenesis.
人类生命可以被描述为一个受精卵的克隆发育过程。在这个克隆体的细胞增殖过程中，会出现其他一些癌症特异性突变。假设一生中产生约10¹⁶个细胞；每个细胞世代每个基因的突变频率约为10⁻⁶；细胞大约可以经历60次细胞分裂；并且一生中患癌约一次，那么癌症发生可能依赖于4个癌症特异性突变。与多突变模型相比，4突变模型的优势在于它蕴含了更多可被检验的预测。4突变模型准确地预测了肿瘤的年龄/发病率关系以及癌症在各个器官中的患病率。它还进一步解释了携带遗传性癌症基因的人群中肿瘤发病率的增加；以及众所周知的癌症发生的组织学阶段。
