THE DIFFERENCE BETWEEN BENIGN AND MALIGNANT-TUMORS EXPLAINED WITH THE4-MUTATION PARADIGM FOR CARCINOGENESIS

In recent years a 4-mutation paradigm for carcinogenesis was developed for mutations in tumour suppressor genes. The major tenet of this par adigm 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 characteris tic differences between benign and malignant tumours. We surmise that benign tumour cells are due to 2 or 3 specific ancer mutations, wherea s malignant tumour cells contain 4 specific cancer mutations and 1-3 t umour 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) en capsulation -invasion, (d) metastasis, and (e) the differences in size of benign epithelial and mesenchymal tumours and the relation between tumour size and malignancy.