Koten J W, Neijt J P, Zonnenberg B A, Den Otter W
Department of Pathology, Academical Hospital Utrecht, The Netherlands.
Anticancer Res. 1993 Jul-Aug;13(4):1179-82.
In recent years a 4-mutation paradigm for carcinogenesis was developed for mutations in tumour suppressor genes. The major tenet of this paradigm is that transformation of a normal cell into a malignant cell is the result of an accumulation of a set of 4 specific cancer mutations. In this paper we show that this paradigm can explain the characteristic differences between benign and malignant tumours. We surmise that benign tumour cells are due to 2 or 3 specific cancer mutations, whereas malignant tumour cells contain 4 specific cancer mutations and 1-3 tumour progression mutations. The following characteristics, essential for differentiating benign and malignant tumours, are explained by our paradigm: (a) differentiation--anaplasia, (b) rate of growth, (c) encapsulation--invasion, (d) metastasis, and (e) the differences in size of benign epithelial and mesenchymal tumours and the relation between tumour size and malignancy.
近年来，针对肿瘤抑制基因的突变，形成了一种致癌作用的四突变模式。该模式的主要原则是，正常细胞转变为恶性细胞是一组4种特定癌症突变积累的结果。在本文中，我们表明这种模式可以解释良性肿瘤和恶性肿瘤之间的特征差异。我们推测，良性肿瘤细胞是由2种或3种特定癌症突变导致的，而恶性肿瘤细胞则包含4种特定癌症突变和1 - 3种肿瘤进展突变。我们的模式解释了以下对于区分良性和恶性肿瘤至关重要的特征：(a)分化——间变，(b)生长速率，(c)包膜形成——侵袭，(d)转移，以及(e)良性上皮和间充质肿瘤大小的差异以及肿瘤大小与恶性程度之间的关系。
