title: The difference between benign and malignant tumours explained with the 4-mutation paradigm for carcinogenesis.
abstract: 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.
authors.affiliation: Department of Pathology, Academical Hospital Utrecht, The Netherlands.
authors.forename: J W
authors.initials: JW
authors.lastname: Koten
authors.forename: J P
authors.initials: JP
authors.lastname: Neijt
authors.forename: B A
authors.initials: BA
authors.lastname: Zonnenberg
authors.forename: W
authors.initials: W
authors.lastname: Den Otter
mesh_terms: D000818:Animals; D002455:Cell Division; D016147:Genes, Tumor Suppressor; D006801:Humans; D008957:Models, Genetic; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology